Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • Rights and Permissions
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons

User menu

  • Subscribe
  • My alerts
  • Log in
  • Log out

Search

  • Advanced search
The Journal of Immunology
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons
  • Subscribe
  • My alerts
  • Log in
  • Log out
The Journal of Immunology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • Rights and Permissions
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Follow The Journal of Immunology on Twitter
  • Follow The Journal of Immunology on RSS

Cutting Edge: B Cells Are Essential for Protective Immunity against Salmonella Independent of Antibody Secretion

Minelva R. Nanton, Sing Sing Way, Mark J. Shlomchik and Stephen J. McSorley
J Immunol December 15, 2012, 189 (12) 5503-5507; DOI: https://doi.org/10.4049/jimmunol.1201413
Minelva R. Nanton
Department of Pediatric Infectious Disease, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota Medical School–Twin Cities, Minneapolis, MN 55455;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sing Sing Way
Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark J. Shlomchik
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06510;Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen J. McSorley
Department of Anatomy, Physiology and Cell Biology, Center for Comparative Medicine, University of California Davis, Davis, CA 95616
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF
Loading

Abstract

Typhoid fever and nontyphoidal bacteremia caused by Salmonella remain critical human health problems. B cells are required for protective immunity to Salmonella, but the mechanism of protection remains unclear. In this study, we immunized wild-type, B cell–deficient, Ab-deficient, and class-switched Ab-deficient mice with attenuated Salmonella and examined protection against secondary infection. As expected, wild-type mice were protected and B cell–deficient mice succumbed to secondary infection. Interestingly, mice with B cells but lacking secreted Ab or class-switched Ab had little deficiency in resistance to Salmonella infection. The susceptibility of B cell–deficient mice correlated with marked reductions in CD4 T cell IFN-γ production after secondary infection. Taken together, these data suggest that the primary role of B cells in acquired immunity to Salmonella is via the development of protective T cell immunity.

Introduction

Typhoid fever is caused by infection with Salmonella typhi and is a serious health concern worldwide, causing an estimated 21 million cases and 216,000 deaths per year (1). Nontyphoidal salmonellosis (NTS) is caused by other Salmonella serovars and is a growing problem among HIV-infected adults and HIV-negative children in Africa and Asia (2–5). Currently, there are two vaccines for typhoid fever that each provide limited protection but are not widely used in endemic areas (6, 7). There is no available vaccine for NTS, although numerous target Ags have recently been defined (8). The development of novel, effective vaccines for typhoid and NTS requires greater understanding of Salmonella-specific T and B cell responses (9).

Immunity to Salmonella is studied using a well-established murine model of typhoid, in which Salmonella typhimurium causes fatal disseminated disease in susceptible, Nramps mice (10, 11). After oral infection, Salmonella can gain access to the mammalian host by invading M cells in the Peyer’s patches of the small intestine (10). Salmonella subsequently disseminates via the lymphatic system and replicates within phagocytic cells of the spleen, liver, and bone marrow. Salmonella actively inhibits phagolysosomal fusion, and infected macrophages require activation via IFN-γ to kill bacteria (12). Salmonella-specific Th1 cells that produce IFN-γ are essential for controlling bacterial growth, and mice lacking αβ CD4 T cells, Th1 cells, or IFN-γ eventually succumb to primary infection with attenuated bacteria (13, 14). Patients with primary genetic deficiencies in IL-12 or IFN-γ receptor signaling suffer from repeated disseminated Salmonella infections (15, 16). Thus, Th1 cells play an important role in mediating protective immunity in both human and murine salmonellosis.

The resolution of primary Salmonella infection confers robust protective immunity against secondary challenge. CD4 T cells are essential for this acquired resistance, and depletion of CD4 T cells eliminates the protective effect of vaccination with attenuated Salmonella (17). More surprisingly, for an intramacrophage infection, B cells are also essential for acquired immunity to Salmonella, and immunized B cell–deficient mice display enhanced susceptibility to secondary infection (18–20). However, the protective role of Abs in secondary immunity is somewhat controversial. Passive transfer of Abs is reported to be protective in some studies, whereas others have observed no protective effect (18, 19, 21). Furthermore, neither IgA nor mucosal Igs are required for protective immunity to Salmonella (8, 22). B cells can contribute to protective immunity via Ag presentation to Salmonella-specific Th1 cells (18, 23) or as an important source of inflammatory cytokines during infection (24, 25). However, it remains unclear whether the contribution of B cells to protective immunity is largely mediated by Ab-dependent or Ab-independent mechanisms.

In this study, we examined the role of B cells in protection against infection with virulent Salmonella using transgenic mouse strains that lack B cells, class-switched Ab, or Ab secretion and demonstrate that Ab production is largely dispensable for protection against secondary Salmonella infection. In contrast, B cells are required for optimal priming of Salmonella-specific Th1 cells that mediate bacterial clearance.

Materials and Methods

Mice

BALB/c (wild-type) and JhD/BALB/c (B cell–deficient) mice (National Cancer Institute, Frederick, MD) were used at 6–12 wk age. Transgenic membrane and secretory (m+s) IgM and membrane IgM (mIgM) use the B1–8 H chain, have a restricted BCR repertoire, were maintained on a JhD/BALB/c background (26). Transgenic mice were intercrossed with JhD/BALB/c mice and were used at 6–12 wk age. Homozygosity at the JHD locus was maintained by interbreeding with JhD mice, and PCR screening of the mIgM H chain was done using the following primers: Vh186.2 5′, CTACTGGATGCACTGGGTGA and Vh186.2 3′, TTGGCCCCAGTAGTCAAAGTA. All mice were housed in specific pathogen-free conditions for breeding and experimentation.

Bacteria and infection

Attenuated S. typhimurium BRD509 (ΔaroA/ΔaroD) and parental virulent strain SL1344 were grown overnight in Luria–Bertani broth and diluted in PBS after estimating bacterial counts by spectrophotometry. Mice were immunized i.v. with 5 × 105 BRD509 and challenged orally with 5 × 107 SL1344 after oral administration of 100 μl 5% NaHCO3. Infection doses were confirmed by plating serial dilutions onto MacConkey agar plates. Any moribund infected mice were euthanized as stipulated in our Institutional Animal Care and Use Committee protocol. Bacterial growth in vivo was calculated by plating serial dilutions of organ homogenates onto MacConkey agar, and bacterial counts were determined after overnight incubation at 37°C.

Detection of in vivo cytokine production and flow cytometry

Salmonella-specific CD4 and CD8 T cell responses were visualized as previously described (27). Immunized mice were injected i.v. with 1 × 108 heat-killed S. typhimurium (HKST) and spleens were harvested 3 or 5 h later. A single-cell suspension was surface stained using FITC-, PE-, PE-Cy5–, PE-Cy7-, allophycocyanin-, eF450-, AF700-, and allophycocyanin-eF780–conjugated Abs to CD3, CD4, CD8, Gr-1, CD11c, CD11b, F4/80, B220, and CD44 in Fc block (spent 24G2 supernatant, 2% rat serum, 2% mouse serum). Cells were fixed, permeabilized, and stained intracellularly using PE-conjugated anti–IFN-γ. All staining reagents were purchased from BD Biosciences (San Jose, CA) or eBioscience (San Diego, CA). Samples were analyzed by flow cytometry using a FACSCanto, and data were analyzed using FlowJo software (Tree Star).

Salmonella-specific Ab response

Blood was collected by retro-orbital bleeding, and sera were prepared and stored at −20°C. Salmonella-specific IgM and IgG Abs were measured by ELISA, as previously described (27).

Statistical analysis

Statistical analysis was performed using unpaired t tests (Prism 4; GraphPad Software, La Jolla, CA). Survival data were compared using a log-rank (Mantel–Cox) test (Prism 4). Statistical differences between groups are delineated as follows: *p < 0.05, **p < 0.01, and ***p < 0.001.

Results and Discussion

Class-switched Abs are not required for secondary protection against Salmonella

Defining protective immune responses to Salmonella infection is a prerequisite for development of new effective vaccines against typhoid and NTS (10). Although CD4 T cells are critical for protective immunity to Salmonella, the contribution of B cells has not been clearly defined. Salmonella-specific Ab production, inflammatory cytokine production, and direct Ag presentation to T cells have each been proposed as mechanisms to explain the protective role of B cells during secondary infection (18, 19, 23, 24, 28). We sought to investigate whether B cells provide secondary protective immunity against Salmonella primarily in an Ab-dependent or -independent manner. Given previous data showing that serum transfer can protect against Salmonella (19), but that neither IgA nor mucosal Ig is required (8), we hypothesized that systemic IgG is essential for secondary clearance of bacteria. To test this hypothesis, we examined immunity in B cell–deficient mice (JhD), transgenic mice with B cells that cannot class switch or secrete Ab (mIgM), and mice with B cells that cannot class switch but are able to secrete IgM (m+s IgM) (26). Although the mIgM and m+s IgM transgenic mice have a restricted BCR repertoire, they do not have significant deviations in naive B cell and T cell subsets (Supplemental Fig. 1A–D and Ref. 29). All four strains (wild-type, B cell–deficient, mIgM, and m+s IgM mice) survived vaccination with attenuated S. typhimurium and had largely cleared bacteria from the spleen 44 d later (Supplemental Fig. 1E). This confirmed previous reports that resolution of primary infection with attenuated Salmonella does not require B cells (18, 19).

To examine acquired immunity to secondary Salmonella infection, naive and immunized mice from all four strains were challenged orally with virulent S. typhimurium (Fig. 1A). Regardless of the B cell compartment, all naive mice succumbed to primary infection with virulent Salmonella at a similar rate (Fig. 1A). In contrast, immunized wild-type mice resisted secondary infection with virulent Salmonella, whereas B cell–deficient mice succumbed to secondary challenge (Fig. 1A). Surprisingly, m+s IgM mice that lack class-switched Ab also survived secondary infection with Salmonella, demonstrating a similar degree of protective immunity to wild-type mice (Fig. 1A). Furthermore, most mIgM mice that lack all secreted Abs were resistant to secondary Salmonella infection. However, ∼25% of these mice eventually died of infection, and this was statistically different from the survival of wild-type and B cell–deficient mice (Fig. 1A). Taken together, these data confirm that B cells are essential for resistance to secondary infection with virulent Salmonella, and they surprisingly demonstrate that production of class-switched Abs is not required for protective immunity. Additionally, although secreted IgM Abs may contribute to secondary protection, the mechanism of B cell–mediated protection against secondary Salmonella infection is largely Ab-independent in this vaccination and rechallenge model.

FIGURE 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
FIGURE 1.

Class-switched Abs are not necessary for immunity to Salmonella. (A) Naive wild-type, JhD, m+s IgM, and mIgM mice were infected orally with 5 × 107 S. typhimurium (SL1344) and survival was monitored. Wild-type, JhD, m+s IgM, and mIgM mice were immunized i.v. with 5 × 105 S. typhimurium (BRD509 ΔaroA/ΔaroD). Forty-two to 66 d later, mice were challenged orally with 5 × 107 S. typhimurium (SL1344) and survival was monitored. Data are pooled from three separate experiments and show the percentage of surviving mice in each group. The total number of mice is indicated. Survival of immunized wild-type, m+s IgM, and mIgM mice was statistically different (***p < 0.001) from JhD mice using a log-rank (Mantel–Cox) test. Survival of mIgM was also statistically different by log-rank test when compared with wild-type mice but not when compared with m+s IgM mice (*p < 0.05). (B) Mice were immunized i.v. with 5 × 105 BRD509, and at day 42 they were challenged orally with 5 × 107 SL1344 and serum was collected 9 d later. Data show levels of heat-killed Salmonella-specific IgM and IgG as determined by ELISA (n = 4–5 mice/group).

Given these findings, it was important to confirm the absence of circulating Salmonella-specific Ab in each B cell–deficient strain examined above. Serum was collected 9 d after secondary infection, and Salmonella-specific Ab responses were examined. Nine days after secondary infection, both wild-type mice and IgM Ab only (m+s IgM) mice had modest levels of circulating Salmonella-specific IgM (Fig. 1B), but only wild-type mice developed Salmonella-specific IgG (Fig. 1B). These results confirm that only wild-type mice produced a class-switched Ab response to Salmonella, but that IgM Ab only mice developed low Salmonella-specific IgM responses during secondary infection.

Secondary bacterial clearance does not require class-switched Abs

Given the fact that mice lacking all Abs had a 25% death rate following virulent challenge, it seemed likely that bacterial clearance was hindered at late time points in these mice, perhaps because IgM is required for clearance from a particularly persistent anatomical site such as the mesenteric lymph nodes (30). Thus, we examined the rate of bacterial clearance in immunized mice lacking B cells, class-switched Abs, or all Abs. Three days after secondary infection, wild-type mice had lower bacterial loads in the spleen than did B cell–deficient mice (Fig. 2A), demonstrating that B cells are required for rapid secondary clearance of bacteria. At this early time point, no significant differences were apparent between Ab-deficient strains and B cell–deficient mice, but Ab-deficient mice had a trend toward lower CFUs in the spleen (Fig. 2A). No significant differences were detected in liver CFUs at this same early time point (Fig. 2B). Nine days after secondary infection, mice lacking B cells had much higher bacterial loads in both the spleen and liver compared with wild-type mice (Fig. 2). In marked contrast, mIgM and m+s IgM mice had lower CFUs in both spleen and liver (Fig. 2). Taken together, these data demonstrate that the rate of bacterial clearance during secondary infection is largely unaffected by the absence of Abs, despite a requirement for B cells. This finding contrasts with prior studies that showed a protective effect of serum transfer (19, 21). However, these studies were not designed to test an Ab-independent role of B cells, and both studies described protection against low dose challenge. Our finding has broad implications because the measurement of circulating Ig is often used as an indicator of vaccine efficacy.

FIGURE 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
FIGURE 2.

Rapid bacterial clearance does not require Abs. (A and B) Mice were immunized i.v. with 5 × 105 BRD509 and 42–66 d later challenged orally with 5 × 107 SL1344. Three and 9 d later bacterial counts were determined in (A) spleen and (B) liver. Data show mean log10 CFUs per organ (n = 6–26 mice per group/time point; *p < 0.05, **p < 0.01, ***p < 0.001).

B cell–deficient mice have reduced CD4 T cell responses to Salmonella

It is clear from previous work that secretion of IFN-γ by Th1 cells is critical for the resolution of Salmonella infections (14, 31). We confirmed this by depleting CD4 and CD8 T cells in immunized wild-type mice and challenging them with a virulent strain of Salmonella. T cell depletion caused a significant increase in bacterial loads during secondary infection (Supplemental Fig. 2A). It has been suggested that Abs can enhance T cell responses to Salmonella by allowing bacterial uptake via Fc receptors on dendritic cells (32). B cells also can present Ag and secrete cytokines that shape the development of protective T cell responses. Thus, we examined the effect of B cell or Ab deficiency on the generation of Salmonella-specific Th1 cells.

Wild-type, B cell–deficient, m+s IgM, and mIgM mice were immunized with attenuated Salmonella, and Salmonella-specific CD4 T cell responses were examined 42 d later. As previously reported (33, 34), immunized wild-type mice had a large population of CD4 T cells that produced IFN-γ in response to HKST stimulation (Fig. 3A, Supplemental Fig. 2B). In marked contrast, immunized B cell–deficient mice had lower numbers of IFN-γ–producing Th1 cells in response to HKST (Fig. 3A, Supplemental Fig. 2B). This difference was Ab-independent, as immunized m+s IgM and mIgM mice had similar levels of IFN-γ–producing CD4 T cells as did wild-type mice (Fig. 3A, Supplemental Fig. 2B). In fact, mIgM mice, which lack all secreted Abs, had a larger population of Salmonella-specific IFN-γ–producing CD4 T cells. Interestingly, IFN-γ–producing CD8 T cells were also slightly reduced in immunized B cell–deficient mice, but this was not statistically significant (Fig. 3B, Supplemental Fig. 2B). Taken together, these data indicate that B cells, but not Abs, are required for shaping the development of protective CD4 Th1 responses to Salmonella. A similar role for B cells has been reported in other infection models such as lymphocytic choriomeningitis virus and Pneumocystis (35, 36). Although B cells may directly present Ag and drive Salmonella-specific Th1 responses, a recent study demonstrated that B cell production of IL-6 is important for maximal Th17 responses, and B cell production of IFN-γ contributed to Th1 development (24). A recent study has also shown that B cells can negatively affect secondary responses to Salmonella infection via an MyD88- and IL-10–dependent mechanism (37). Thus, B cells likely contribute to protective CD4 responses via Ag presentation and production of specific cytokines that drive effector lineage commitment during primary responses. It is not yet clear whether these required B cells are necessarily Salmonella-specific, but the limited B cell repertoire in IgM only mice and in no Ab mice did not affect protective immunity. We also attempted to address this issue using in vitro restimulation and B cell tetramer pull-down experiments in previously infected mice, but we did not detect an elevated frequency of Salmonella-specific B cells using either of these approaches. However, it remains possible that expanded Salmonella-specific B cells contribute to immunity to secondary infection.

FIGURE 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
FIGURE 3.

Ab is not required for optimal Salmonella-specific Th1 cells. (A and B) Mice were immunized i.v. with 5 × 105 BRD509 and 42–47 d later injected i.v. with 108 HKST to stimulate T cell responses. Bar graphs showing mean number of (A) CD4 or (B) CD8 T cells producing IFN-γ after stimulation with HKST (**p < 0.01, ***p < 0.001).

Collectively, our data demonstrate that Ab production plays only a minor role in Salmonella immunity in our live vaccination model, whereas B cells are required for the development of protective T cell immunity. These findings will be important for the development of new effective vaccines against typhoid and NTS.

Disclosures

The authors have no financial conflicts of interest.

Footnotes

  • This work was supported by National Institutes of Health Grants AI091298 (to M.R.N.), AI087830 (to S.S.W.), AI043603 (to M.J.S.), AI055743 and AI073672 (to S.J.M.), and T32 GM008244 (to the University of Minnesota Medical Scientist Training Program).

  • The online version of this article contains supplemental material.

  • Abbreviations used in this article:

    HKST
    heat-killed Salmonella typhimurium
    mIgM
    membrane IgM
    m+s IgM
    membrane and secretory IgM
    NTS
    nontyphoidal salmonellosis.

  • Received May 25, 2012.
  • Accepted October 18, 2012.
  • Copyright © 2012 by The American Association of Immunologists, Inc.

References

  1. ↵
    1. Crump J. A.,
    2. S. P. Luby,
    3. E. D. Mintz
    . 2004. The global burden of typhoid fever. Bull. World Health Organ. 82: 346–353.
    OpenUrlPubMed
  2. ↵
    1. Gordon M. A.,
    2. A. M. Kankwatira,
    3. G. Mwafulirwa,
    4. A. L. Walsh,
    5. M. J. Hopkins,
    6. C. M. Parry,
    7. E. B. Faragher,
    8. E. E. Zijlstra,
    9. R. S. Heyderman,
    10. M. E. Molyneux
    . 2010. Invasive non-typhoid salmonellae establish systemic intracellular infection in HIV-infected adults: an emerging disease pathogenesis. Clin. Infect. Dis. 50: 953–962.
    OpenUrlAbstract/FREE Full Text
    1. Graham S. M.
    2010. Nontyphoidal salmonellosis in Africa. Curr. Opin. Infect. Dis. 23: 409–414.
    OpenUrlCrossRefPubMed
    1. MacLennan C. A.,
    2. J. J. Gilchrist,
    3. M. A. Gordon,
    4. A. F. Cunningham,
    5. M. Cobbold,
    6. M. Goodall,
    7. R. A. Kingsley,
    8. J. J. van Oosterhout,
    9. C. L. Msefula,
    10. W. L. Mandala,
    11. et al
    . 2010. Dysregulated humoral immunity to nontyphoidal Salmonella in HIV-infected African adults. Science 328: 508–512.
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. MacLennan C. A.,
    2. E. N. Gondwe,
    3. C. L. Msefula,
    4. R. A. Kingsley,
    5. N. R. Thomson,
    6. S. A. White,
    7. M. Goodall,
    8. D. J. Pickard,
    9. S. M. Graham,
    10. G. Dougan,
    11. et al
    . 2008. The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children. J. Clin. Invest. 118: 1553–1562.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Black R. E.,
    2. M. M. Levine,
    3. C. Ferreccio,
    4. M. L. Clements,
    5. C. Lanata,
    6. J. Rooney,
    7. R. Germanier,
    8. Chilean Typhoid Committee
    . 1990. Efficacy of one or two doses of Ty21a Salmonella typhi vaccine in enteric-coated capsules in a controlled field trial. Vaccine 8: 81–84.
    OpenUrlCrossRefPubMed
  5. ↵
    1. Fraser A.,
    2. M. Paul,
    3. E. Goldberg,
    4. C. J. Acosta,
    5. L. Leibovici
    . 2007. Typhoid fever vaccines: systematic review and meta-analysis of randomised controlled trials. Vaccine 25: 7848–7857.
    OpenUrlCrossRefPubMed
  6. ↵
    1. Lee S. J.,
    2. L. Liang,
    3. S. Juarez,
    4. M. R. Nanton,
    5. E. N. Gondwe,
    6. C. L. Msefula,
    7. M. A. Kayala,
    8. F. Necchi,
    9. J. N. Heath,
    10. P. Hart,
    11. et al
    . 2012. Identification of a common immune signature in murine and human systemic salmonellosis. Proc. Natl. Acad. Sci. USA 109: 4998–5003.
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Pasetti M. F.,
    2. J. K. Simon,
    3. M. B. Sztein,
    4. M. M. Levine
    . 2011. Immunology of gut mucosal vaccines. Immunol. Rev. 239: 125–148.
    OpenUrlCrossRefPubMed
  8. ↵
    1. Griffin A. J.,
    2. S. J. McSorley
    . 2011. Development of protective immunity to Salmonella, a mucosal pathogen with a systemic agenda. Mucosal Immunol. 4: 371–382.
    OpenUrlCrossRefPubMed
  9. ↵
    1. Tsolis R. M.,
    2. M. N. Xavier,
    3. R. L. Santos,
    4. A. J. Bäumler
    . 2011. How to become a top model: impact of animal experimentation on human Salmonella disease research. Infect. Immun. 79: 1806–1814.
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Mastroeni P.,
    2. A. Grant,
    3. O. Restif,
    4. D. Maskell
    . 2009. A dynamic view of the spread and intracellular distribution of Salmonella enterica. Nat. Rev. Microbiol. 7: 73–80.
    OpenUrlCrossRefPubMed
  11. ↵
    1. Hess J.,
    2. C. Ladel,
    3. D. Miko,
    4. S. H. Kaufmann
    . 1996. Salmonella typhimurium aroA- infection in gene-targeted immunodeficient mice: major role of CD4+ TCR-αβ cells and IFN-γ in bacterial clearance independent of intracellular location. J. Immunol. 156: 3321–3326.
    OpenUrlAbstract
  12. ↵
    1. Ravindran R.,
    2. J. Foley,
    3. T. Stoklasek,
    4. L. H. Glimcher,
    5. S. J. McSorley
    . 2005. Expression of T-bet by CD4 T cells is essential for resistance to Salmonella infection. J. Immunol. 175: 4603–4610.
    OpenUrlAbstract/FREE Full Text
  13. ↵
    1. Dorman S. E.,
    2. S. M. Holland
    . 2000. Interferon-γ and interleukin-12 pathway defects and human disease. Cytokine Growth Factor Rev. 11: 321–333.
    OpenUrlCrossRefPubMed
  14. ↵
    1. MacLennan C.,
    2. C. Fieschi,
    3. D. A. Lammas,
    4. C. Picard,
    5. S. E. Dorman,
    6. O. Sanal,
    7. J. M. MacLennan,
    8. S. M. Holland,
    9. T. H. Ottenhoff,
    10. J. L. Casanova,
    11. D. S. Kumararatne
    . 2004. Interleukin (IL)-12 and IL-23 are key cytokines for immunity against Salmonella in humans. J. Infect. Dis. 190: 1755–1757.
    OpenUrlAbstract/FREE Full Text
  15. ↵
    1. Nauciel C.
    1990. Role of CD4+ T cells and T-independent mechanisms in acquired resistance to Salmonella typhimurium infection. J. Immunol. 145: 1265–1269.
    OpenUrlAbstract
  16. ↵
    1. Mastroeni P.,
    2. C. Simmons,
    3. R. Fowler,
    4. C. E. Hormaeche,
    5. G. Dougan
    . 2000. Igh-6−/− (B-cell-deficient) mice fail to mount solid acquired resistance to oral challenge with virulent Salmonella enterica serovar typhimurium and show impaired Th1 T-cell responses to Salmonella antigens. Infect. Immun. 68: 46–53.
    OpenUrlAbstract/FREE Full Text
  17. ↵
    1. McSorley S. J.,
    2. M. K. Jenkins
    . 2000. Antibody is required for protection against virulent but not attenuated Salmonella enterica serovar typhimurium. Infect. Immun. 68: 3344–3348.
    OpenUrlAbstract/FREE Full Text
  18. ↵
    1. Mittrücker H. W.,
    2. B. Raupach,
    3. A. Köhler,
    4. S. H. Kaufmann
    . 2000. Cutting edge: role of B lymphocytes in protective immunity against Salmonella typhimurium infection. J. Immunol. 164: 1648–1652.
    OpenUrlAbstract/FREE Full Text
  19. ↵
    1. Mastroeni P.,
    2. B. Villarreal-Ramos,
    3. C. E. Hormaeche
    . 1993. Adoptive transfer of immunity to oral challenge with virulent salmonellae in innately susceptible BALB/c mice requires both immune serum and T cells. Infect. Immun. 61: 3981–3984.
    OpenUrlAbstract/FREE Full Text
  20. ↵
    1. Wijburg O. L.,
    2. T. K. Uren,
    3. K. Simpfendorfer,
    4. F. E. Johansen,
    5. P. Brandtzaeg,
    6. R. A. Strugnell
    . 2006. Innate secretory antibodies protect against natural Salmonella typhimurium infection. J. Exp. Med. 203: 21–26.
    OpenUrlAbstract/FREE Full Text
  21. ↵
    1. Ugrinovic S.,
    2. N. Ménager,
    3. N. Goh,
    4. P. Mastroeni
    . 2003. Characterization and development of T-Cell immune responses in B-cell-deficient (Igh-6−/−) mice with Salmonella enterica serovar Typhimurium infection. Infect. Immun. 71: 6808–6819.
    OpenUrlAbstract/FREE Full Text
  22. ↵
    1. Barr T. A.,
    2. S. Brown,
    3. P. Mastroeni,
    4. D. Gray
    . 2010. TLR and B cell receptor signals to B cells differentially program primary and memory Th1 responses to Salmonella enterica. J. Immunol. 185: 2783–2789.
    OpenUrlAbstract/FREE Full Text
  23. ↵
    1. Barr T. A.,
    2. S. Brown,
    3. P. Mastroeni,
    4. D. Gray
    . 2009. B cell intrinsic MyD88 signals drive IFN-γ production from T cells and control switching to IgG2c. J. Immunol. 183: 1005–1012.
    OpenUrlAbstract/FREE Full Text
  24. ↵
    1. Chan O. T.,
    2. L. G. Hannum,
    3. A. M. Haberman,
    4. M. P. Madaio,
    5. M. J. Shlomchik
    . 1999. A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus. J. Exp. Med. 189: 1639–1648.
    OpenUrlAbstract/FREE Full Text
  25. ↵
    1. Griffin A.,
    2. D. Baraho-Hassan,
    3. S. J. McSorley
    . 2009. Successful treatment of bacterial infection hinders development of acquired immunity. J. Immunol. 183: 1263–1270.
    OpenUrlAbstract/FREE Full Text
  26. ↵
    1. Cunningham A. F.,
    2. F. Gaspal,
    3. K. Serre,
    4. E. Mohr,
    5. I. R. Henderson,
    6. A. Scott-Tucker,
    7. S. M. Kenny,
    8. M. Khan,
    9. K. M. Toellner,
    10. P. J. Lane,
    11. I. C. MacLennan
    . 2007. Salmonella induces a switched antibody response without germinal centers that impedes the extracellular spread of infection. J. Immunol. 178: 6200–6207.
    OpenUrlAbstract/FREE Full Text
  27. ↵
    1. Hannum L. G.,
    2. A. M. Haberman,
    3. S. M. Anderson,
    4. M. J. Shlomchik
    . 2000. Germinal center initiation, variable gene region hypermutation, and mutant B cell selection without detectable immune complexes on follicular dendritic cells. J. Exp. Med. 192: 931–942.
    OpenUrlAbstract/FREE Full Text
  28. ↵
    1. Griffin A. J.,
    2. L. X. Li,
    3. S. Voedisch,
    4. O. Pabst,
    5. S. J. McSorley
    . 2011. Dissemination of persistent intestinal bacteria via the mesenteric lymph nodes causes typhoid relapse. Infect. Immun. 79: 1479–1488.
    OpenUrlAbstract/FREE Full Text
  29. ↵
    1. Mastroeni P.,
    2. B. Villarreal-Ramos,
    3. C. E. Hormaeche
    . 1992. Role of T cells, TNFα and IFNγ in recall of immunity to oral challenge with virulent salmonellae in mice vaccinated with live attenuated aro- Salmonella vaccines. Microb. Pathog. 13: 477–491.
    OpenUrlCrossRefPubMed
  30. ↵
    1. Tobar J. A.,
    2. P. A. González,
    3. A. M. Kalergis
    . 2004. Salmonella escape from antigen presentation can be overcome by targeting bacteria to Fc gamma receptors on dendritic cells. J. Immunol. 173: 4058–4065.
    OpenUrlAbstract/FREE Full Text
  31. ↵
    1. Griffin A. J.,
    2. S. J. McSorley
    . 2011. Generation of Salmonella-specific Th1 cells requires sustained antigen stimulation. Vaccine 29: 2697–2704.
    OpenUrlCrossRefPubMed
  32. ↵
    1. Srinivasan A.,
    2. J. Foley,
    3. S. J. McSorley
    . 2004. Massive number of antigen-specific CD4 T cells during vaccination with live attenuated Salmonella causes interclonal competition. J. Immunol. 172: 6884–6893.
    OpenUrlAbstract/FREE Full Text
  33. ↵
    1. Whitmire J. K.,
    2. M. S. Asano,
    3. S. M. Kaech,
    4. S. Sarkar,
    5. L. G. Hannum,
    6. M. J. Shlomchik,
    7. R. Ahmed
    . 2009. Requirement of B cells for generating CD4+ T cell memory. J. Immunol. 182: 1868–1876.
    OpenUrlAbstract/FREE Full Text
  34. ↵
    1. Lund F. E.,
    2. M. Hollifield,
    3. K. Schuer,
    4. J. L. Lines,
    5. T. D. Randall,
    6. B. A. Garvy
    . 2006. B cells are required for generation of protective effector and memory CD4 cells in response to Pneumocystis lung infection. J. Immunol. 176: 6147–6154.
    OpenUrlAbstract/FREE Full Text
  35. ↵
    1. Neves P.,
    2. V. Lampropoulou,
    3. E. Calderon-Gomez,
    4. T. Roch,
    5. U. Stervbo,
    6. P. Shen,
    7. A. A. Kühl,
    8. C. Loddenkemper,
    9. M. Haury,
    10. S. A. Nedospasov,
    11. et al
    . 2010. Signaling via the MyD88 adaptor protein in B cells suppresses protective immunity during Salmonella typhimurium infection. Immunity 33: 777–790.
    OpenUrlCrossRefPubMed
View Abstract
PreviousNext
Back to top

In this issue

The Journal of Immunology: 189 (12)
The Journal of Immunology
Vol. 189, Issue 12
15 Dec 2012
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Advertising (PDF)
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Immunology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Cutting Edge: B Cells Are Essential for Protective Immunity against Salmonella Independent of Antibody Secretion
(Your Name) has forwarded a page to you from The Journal of Immunology
(Your Name) thought you would like to see this page from the The Journal of Immunology web site.
Citation Tools
Cutting Edge: B Cells Are Essential for Protective Immunity against Salmonella Independent of Antibody Secretion
Minelva R. Nanton, Sing Sing Way, Mark J. Shlomchik, Stephen J. McSorley
The Journal of Immunology December 15, 2012, 189 (12) 5503-5507; DOI: 10.4049/jimmunol.1201413

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Cutting Edge: B Cells Are Essential for Protective Immunity against Salmonella Independent of Antibody Secretion
Minelva R. Nanton, Sing Sing Way, Mark J. Shlomchik, Stephen J. McSorley
The Journal of Immunology December 15, 2012, 189 (12) 5503-5507; DOI: 10.4049/jimmunol.1201413
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results and Discussion
    • Disclosures
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Cutting Edge: Involvement of the Immunoreceptor CD300c2 on Alveolar Macrophages in Bleomycin-Induced Lung Fibrosis
  • Cutting Edge: TCR Signal Strength Regulates Acetyl-CoA Metabolism via AKT
  • Cutting Edge: Elevated Glycolytic Metabolism Limits the Formation of Memory CD8+ T Cells in Early Life
Show more CUTTING EDGE

Similar Articles

Navigate

  • Home
  • Current Issue
  • Next in The JI
  • Archive
  • Brief Reviews
  • Pillars of Immunology
  • Translating Immunology

For Authors

  • Submit a Manuscript
  • Instructions for Authors
  • About the Journal
  • Journal Policies
  • Editors

General Information

  • Advertisers
  • Subscribers
  • Rights and Permissions
  • Accessibility Statement
  • Public Access
  • Privacy Policy
  • Disclaimer

Journal Services

  • Email Alerts
  • RSS Feeds
  • ImmunoCasts
  • Twitter

Copyright © 2019 by The American Association of Immunologists, Inc.

Print ISSN 0022-1767        Online ISSN 1550-6606