The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Edelson, B. T.
Right arrow Articles by Unanue, E. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Edelson, B. T.
Right arrow Articles by Unanue, E. R.
The Journal of Immunology, 1999, 163: 4087-4090.
Copyright © 1999 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Paradigm Revisited: Antibody Provides Resistance to Listeria Infection1

Brian T. Edelson*, Pascale Cossart{dagger} and Emil R. Unanue2,*

* Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110; and {dagger} Unite des Interactions Bacteries Cellules, Institut Pasteur, Paris, France


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Listeriolysin O (LLO) is a secreted pore-forming toxin of the facultative intracellular bacterium Listeria monocytogenes. We assessed the ability of a murine anti-LLO mAb to affect the course of infection in mice challenged with Listeria. This mAb was previously shown to be capable of neutralizing LLO-mediated pore formation in vitro, and here we show that the passive administration of this Ab to mice before infection provides increased resistance. Mice treated with the mAb were protected from a lethal challenge with virulent Listeria and showed a significant reduction in Listeria burden during the first hours to days postinfection. These effects of the Ab were independent of host B or T cells, since treatment with the mAb provided enhanced resistance to SCID mice. The titer of anti-LLO Abs during the regular infection of mice with Listeria was found to be low to negative.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The mouse model of Listeria infection has long been used to study the mechanisms of host defense against intracellular bacteria, a process known to require components of both the innate and adaptive immune responses (1). Early studies by G. B. Mackaness and others indicated that serum taken from mice following sublethal infection provided no resistance against Listeria when passively transferred to naive mice (2). At the time of these studies, the specificity of anti-Listeria Abs in this polyclonal serum was not investigated. Because some investigators had also noted the failure of antisera to influence resistance against tuberculosis, the attention was then focused on cellular mechanisms of resistance (reviewed in Ref. 3). Indeed, studies in both experimental models led to the concept of cell-mediated immunity, with the requirement for T lymphocytes and activated macrophages in the acquired resistance to these intracellular bacteria (2, 4, 5, 6).

In the experiments described here, we demonstrate that an Ab to listeriolysin O (LLO)3 provides resistance to Listeria infection. LLO, the Ag recognized by the A4-8 mAb, is a 58-kDa secreted protein of Listeria monocytogenes and an important virulence factor (reviewed in Ref. 7). LLO is a member of the family of thiol-activated pore-forming toxins secreted by numerous Gram-positive bacterial species (8). LLO mediates escape of Listeria from the phagosome of an infected cell, allowing the organism to access the cytosol, where it replicates rapidly and avoids the host cell’s microbicidal actions (9, 10). LLO has also been shown to have numerous exotoxic actions when applied to cells in vitro, although the significance of these cellular responses during in vivo pathogenesis has not been established (11, 12, 13, 14, 15, 16, 17, 18).


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Mice

CB.17 and CB.17-SCID mice were maintained and bred under SPF conditions in the Washington University mouse facility. For infection with Listeria, mice of either sex were used, between 8 and 16 wk of age.

Bacteria

All experiments utilized L. monocytogenes strain EGD. The LD50 of this strain in CB.17 or CB.17-SCID mice is ~1 x 103 organisms. Bacteria was stored as frozen glycerol stocks and thawed once before dilution into pyrogen-free saline for injection into mice.

mAbs and in vivo use

mAbs utilized in this study were the A4-8 mAb (murine anti-LLO, IgG1) and the irrelevant control GIR.208 mAb (murine anti-human IFN-{gamma} receptor, IgG1, a gift of Dr. Robert Schreiber, Washington University, St. Louis, MO). A4-8 was generated by the immunization of mice with purified LLO plus Freund’s adjuvant (19). This mAb was chosen because it had been shown to bind LLO in solution and block both membrane binding by the toxin and subsequent lysis of RBC in vitro. mAbs were purified from ascites using standard methods on protein A-Sepharose (Sigma, St. Louis, MO) and were shown to contain less than 10 endotoxin units per milligram protein by the QCL-1000 endotoxin quantitation kit (BioWhittaker, Walkersville, MD). Ab concentration was determined by the measurement of absorbance at OD 280 (1%:13.5). In most experiments, mice were injected with 1 mg mAb per mouse i.p., 1 day before i.p. infection with Listeria. Following infection, mice were followed for survival for 14 days or sacrificed at various time points postinfection to determine organ Listeria burden. This was done by aseptic removal of the spleen and/or liver, followed by the homogenization of each organ in PBS plus 0.05% TX-100. Serial dilutions of homogenate were plated on brain heart infusion agar, and bacterial CFU were assessed after overnight growth at 37°C.

Assessment of Ab responses to Listeria infection

CB.17 mice were infected three times (intervals of 2 to 4 wk before reinfection) with Listeria, at doses of 5 x 102, 1 x 103, and 1 x 104 organisms i.p. Serum Ab responses to whole Listeria Ag and LLO were measured using the following ELISA protocols. To test for Ab to whole Listeria Ag, Nunc Maxisorp plates (Nunc, Roskilde, Denmark) were coated overnight at 4°C with 1 x 107/well live Listeria in 0.1 M carbonate buffer (pH 8.5). Plates were washed at each step with PBS plus 0.05% Tween 20, blocked with PBS plus 1% BSA for 1 h at room temperature, incubated with serum samples diluted in PBS plus 1% BSA for 2 h at room temperature, and then incubated with secondary Ab (goat anti-mouse IgG-peroxidase; Boehringer-Mannheim, Indianapolis, IN) diluted in PBS plus 1% BSA for 1 h at room temperature. Plates were then treated with 1 mM ABTS in citrate buffer with 0.05% H2O2, and OD 415 was measured. To test for Ab to LLO, an identical ELISA was performed, this time coating the plate initially with 100 ng/well histidine-tagged recombinant LLO (produced in Escherichia coli, a gift of Dr. Daniel Portnoy, University of California, Berkeley, CA (M. M. Gedde and D. A. Portnoy, unpublished observations)). To test whether polyclonal anti-Listeria Abs could provide protection against Listeria infection in vivo, serum was obtained from control CB.17 mice and Listeria immune mice (the same mice whose serum was tested above, serum taken 2 wk following a fourth infection with 1 x 104 Listeria i.p.). Serum was pooled, and crude Ig was obtained by precipitation in 50% saturated ammonium sulfate using standard methods. Naive CB.17 mice were administered 2 mg/mouse of control Ig or immune Ig 1 day before infection with 1 x 104 Listeria i.p. Mice were sacrificed at day 2 postinfection, and organ Listeria burden was assessed as described above.

Statistics

Data were analyzed using GraphPad PRISM software (Version 2.0, GraphPad Software, San Diego, CA). Survival curves were compared using the logrank test, and CFU determinations were compared using the Mann-Whitney test.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Several experiments showed that the anti-LLO mAb A4-8 provided resistance to Listeria, as noted by both the number of organisms in the spleen and liver, and by survival of the mice after infection with relatively high infectious doses. The amount of A4-8 that affected protection was 1 mg per mouse (weight of mice ~25 g). Lower amounts resulted in much less of an effect. In no instance did we find an effect of the control Ab of the same isotype. Representative experiments are indicated in the figures. Fig. 1GoA shows the survival of CB.17 mice administered either the anti-LLO mAb A4-8 or an irrelevant isotype control mAb 1 day before infection with a relatively high dose, 7.5 x 103 Listeria i.p. A second control group was also included, which received no treatment before infection with Listeria. Mice were followed for 14 days postinfection, with the majority of control mice succumbing to infection, mostly on days 4 through 7 (GIR.208 group: 9/10 dead; untreated group: 10/12 dead). The majority of A4-8-treated mice survived infection (3/10 dead), indicating a protective effect of the anti-LLO mAb. In a separate experiment, CB.17 mice were treated with A4-8 or control mAb 1 day before infection with 1 x 103 Listeria i.p. Survivors of this primary infection (A4-8 group: 2/10 dead; GIR.208 group: 5/9 dead) were then challenged with a normally lethal dose of Listeria (5 x 104), and all but one mouse (originally GIR.208 treated) survived this secondary infection, indicating that A4-8 treatment protected and did not affect the ability of mice to generate a memory response to Listeria during primary infection.



View larger version (26K):
[in this window]
[in a new window]
  		FIGURE 1. Anti-LLO mAb enhances survival of immunocompetent and SCID mice after Listeria infection. A, CB.17 mice were administered anti-LLO mAb (n = 10) or control mAb (n = 10), or left untreated (n = 12), 1 day before infection with 7.5 x 103 Listeria i.p. Mice were followed for survival for 14 days postinfection (anti-LLO mAb vs control mAb, p = 0.0014). B, CB.17-SCID mice were administered anti-LLO mAb (n = 9) or control mAb (n = 10) 1 day before infection with 2 x 103 Listeria i.p. mAbs were readministered on days 5 and 10 postinfection. Mice were followed for survival for 14 days postinfection (p = 0.0208).

 
To determine the requirement for B or T cells during Ab-mediated resistance in vivo, a similar experiment was performed in SCID mice, devoid of these cell types due to a genetic mutation in the DNA-PK gene. CB.17-SCID mice were administered A4-8 or the control mAb 1 day before infection with 2 x 103Listeria i.p., and then readministered the same mAb on days 5 and 10 postinfection. At this dose of Listeria, approximately half of the control mice survived infection through day 14 (6/10 dead), while again the majority of A4-8-treated mice survived to this time point (1/9 dead) (Fig. 1GoB). Since SCID mice are known to develop a chronic infection with Listeria due to the lack of T cells, we assessed the surviving mice in this experiment for the presence of Listeria in the spleen and liver on day 14 (20). Both control and anti-LLO-treated survivors were found to harbor similar levels of Listeria in these organs (geometric mean CFU of controls: 9.0 x 102/spleen, 1.3 x 103/liver; of A4-8 treated: 3.3 x 103/spleen, 2.3 x 103/liver), indicating that, while the A4-8 mAb provided enhanced survival in Listeria-infected SCID mice, it was not sufficient in the absence of T cells to bring about sterilizing immunity.

Anti-LLO provided resistance through the limitation of organ Listeria growth during infection. CB.17 mice were administered A4-8 or the control mAb 1 day before infection with 1 x 104 Listeria i.p. At day 2 postinfection, the mice treated with anti-LLO mAb had ~100-fold fewer CFU in the spleens and livers, a very dramatic reduction and the likely explanation for how the Ab provided enhanced survival in the previous experiments (Fig. 2Go, B and C). When a lower dose of Listeria was used (1 x 103) and mice were examined at day 4 postinfection, A4-8-treated mice had no detectable bacteria in the spleen or liver (limit of detection 100 organisms/organ), while control mAb-treated mice had geometric mean CFU of ~104 Listeria/organ. A4-8 also affected Listeria CFU at day 2 postinfection in mice infected with Listeria i.v. (data not shown). In preliminary studies, a nonneutralizing anti-LLO mAb was unable to affect Listeria CFU during Listeria infection, suggesting that neutralization of LLO is important for Ab-mediated resistance. At day 2 postinfection following a dose of 1 x 104 Listeria i.p., mice treated with the E4-3 nonneutralizing mAb to LLO (see Ref. 19) had geometric mean CFU of 1.0 x 105Listeria/organ, while the control mAb-treated mice had geometric mean CFU of 2.8 x 105 Listeria/organ. In this same experiment, mice treated with A4-8 again had ~100-fold fewer CFU/organ, having a geometric mean CFU of 2.5 x 103 Listeria/organ.



View larger version (20K):
[in this window]
[in a new window]
  		FIGURE 2. Passive administration of anti-LLO mAb limits Listeria burden in vivo. A, CB.17 mice were administered anti-LLO mAb (n = 9) or control mAb (n = 9) 1 day before infection with 1 x 106 Listeria i.p. Mice were sacrificed at 6 h postinfection to determine Listeria CFU/spleen. Circles represent individual mice, and bars represent the geometric mean CFU/spleen (p < 0.0001). Results shown are the combination of two identical experiments. B and C, CB.17 mice were administered anti-LLO mAb (n = 5) or control mAb (n = 5) 1 day before infection with 1 x 104 Listeria i.p. Mice were sacrificed at day 2 postinfection to determine Listeria CFU in the (B) spleen and (C) liver. Circles represent individual mice, and bars represent the geometric mean CFU/organ (B, p = 0.0079; C, p = 0.0079). Representative of three experiments with similar results.

 
The effects of the A4-8 mAb could be detected at 6 h postinfection. In pilot experiments, it was determined that to recover reasonable numbers of organisms from the spleen at this very early time point, a dose of 1 x 106 Listeria should be used. At 6 h postinfection, spleen Listeria CFU were already reduced by ~1 log in mice that received the A4-8 mAb (Fig. 2GoA). We interpret this result to mean that anti-LLO mAb can act to reduce Listeria growth in vivo by some very fast-acting mechanism.

To investigate whether anti-LLO Abs are generated as part of the normal immune response to Listeria infection, we performed the following experiment. CB.17 mice were infected with Listeria three times, each time with an increasing number of organisms spaced 2 to 4 wk apart. Following the third infection, serum Ab to LLO was measured in an ELISA assay with plate-bound histidine-tagged recombinant LLO (Fig. 3GoB). Ab responses were minimal, with only a small fraction of the mice showing any anti-LLO Ab at a serum dilution of 1/500. To determine whether the Ab response to LLO was especially low compared with the Ab response to other Listeria Ags, we tested these same serum samples for Ab to whole Listeria Ag in a similar ELISA assay with plate-bound Listeria (Fig. 3GoA). While a few mice showed detectable Ab at a serum dilution of 1/50, again very little Ab was detectable at a serum dilution of 1/500. These results indicate that Ab responses to Listeria Ags, including LLO, are very low in mice following Listeria infection. The Ig from these Listeria-immune mice did not confer passive protection to Listeria (Fig. 3GoC).



View larger version (25K):
[in this window]
[in a new window]
  		FIGURE 3. Infection induces only limited Ab responses to whole Listeria Ag and LLO. A and B, CB.17 mice (n = 13) were infected three times with Listeria and then tested for serum Ab responses by ELISA to (A) whole Listeria Ag or (B) LLO. Responses were compared with preimmune sera taken before infection. Serum was tested at dilutions of 1/50 and 1/500. Circles represent individual mice and bars represent the mean OD at 415 nm. C, CB.17 mice were administered control mAb (n = 5), anti-LLO mAb (n = 5), control Ig (n = 5), or immune Ig (n = 5) (see Materials and Methods for details) 1 day before infection with 1 x 104 Listeria i.p. Mice were sacrificed at day 2 postinfection to determine Listeria CFU/spleen. Bars represent the geometric mean ± SEM (anti-LLO mAb vs control mAb, p = 0.0079, control Ig vs immune Ig, p = 0.8413).

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In this study we demonstrate that the passive administration of a neutralizing mAb to LLO, a secreted pore-forming toxin of the facultative intracellular bacterium L. monocytogenes, can provide resistance to Listeria infection in mice. The mechanism(s) whereby Ab mediates protection is not clear at this point, although the mAb can act very quickly to limit Listeria growth in vivo. Potential mechanisms could include the following: 1) opsonization of bacteria and/or complement activation through the binding of surface associated LLO (this is unlikely since in our ELISA assay the A4-8 mAb recognized whole Listeria only at an Ab concentration of 100 µg/ml); 2) neutralization of LLO inside of the phagosomes of infected cells, leading to the prevention of bacterial escape to the cytosol; or 3) neutralization of the exotoxic functions of LLO during a time when the organism is present in the extracellular environment. Studies are in progress in our laboratory to address these possibilities.

Although Ab can clearly add a component of resistance to listeriosis, it is by no means an absolute requirement. Indeed CD4 and CD8 T cells can confer protective immunity without the need for Ab, a point exemplified in SCID mice, which clear infection after T cell transfer (20). Ab to LLO provided protection to SCID mice but did not allow for the complete clearance of the organism, indicating a necessity for T cells in mediating sterilizing immunity. Thus, we envision a cooperativity in listeriosis of different cells and soluble molecules (cytokines and Ab) to bring about complete resistance.

The surprising finding is that Ab can generate marked protection against listeriosis. Previous studies in which anti-Listeria serum was taken following infection or immunization with killed bacteria and then transferred to naive animals did not demonstrate protection against Listeria infection (2, 21, 22). Our experiments differ from previous studies with immune serum because we have utilized a defined mAb to a particular virulence factor, LLO. In infection models with other intracellular pathogens, mAbs have been shown to provide resistance when polyclonal serum could not (23). This has been explained to be due to a low abundance of serum Ab to protective Ags, or as a result of serum Ab being of an inappropriate isotype to mediate resistance.

Confirming the results of others, we found that the titer of anti-Listeria Abs, particularly anti-LLO Abs, during the normal infection of mice is limited (2, 24). This explains the failure to transfer protection with serum. Why LLO can elicit CD4 and CD8 T cell immunity but a weak B cell response may have to do with the fate of the intact LLO molecules and/or its particular biological features (25, 26). Overall, our studies demonstrate that an Ab to a secreted virulence factor of a facultative intracellular bacterium can provide resistance against infection, and open up the possibility for immunization with such virulence factors as a method for vaccination against intracellular pathogens.


   Acknowledgments
 
We thank Katherine Frederick for technical support, Dr. Robert Schreiber for the GIR.208 mAb, Dr. Daniel Portnoy and Dr. Margaret Gedde for the recombinant LLO expression system, and Dr. Osami Kanagawa and Dr. Hao Shen for advice in many helpful discussions.


   Footnotes
 
1 This work was supported by grants from the National Institutes of Health. Back

2 Address correspondence and reprint requests to Dr. Emil R. Unanue, Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110. E-mail address: Back

3 Abbreviation used in this paper: LLO, listeriolysin O. Back

Received for publication July 13, 1999. Accepted for publication August 6, 1999.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Unanue, E. R.. 1997. Studies in listeriosis show the strong symbiosis between the innate cellular system and the T-cell response. Immunol. Rev. 158:11.[Medline]
  2. Mackaness, G. B.. 1962. Cellular resistance to infection. J. Exp. Med. 116:381.[Abstract]
  3. Glatman-Freedman, A., A. Casadevall. 1998. Serum therapy for tuberculosis revisited: reappraisal of the role of antibody-mediated immunity against Mycobacterium tuberculosis. Clin. Microbiol. Rev. 11:514.[Abstract/Free Full Text]
  4. Miki, K., G. B. Mackaness. 1964. The passive transfer of acquired resistance to Listeria monocytogenes. J. Exp. Med. 120:93.[Abstract]
  5. Mackaness, G. B.. 1964. The immunological basis of acquired cellular resistance. J. Exp. Med. 120:105.[Abstract]
  6. Mackaness, G. B.. 1969. The influence of immunologically committed lymphoid cells on macrophage activity in vivo. J. Exp. Med. 129:973.[Abstract]
  7. Sheehan, B., C. Kocks, S. Dramsi, E. Gouin, A. D. Klarsfeld, J. Mengaud, P. Cossart. 1994. Molecular and genetic determinants of the Listeria monocytogenes infectious process. Curr. Top. Microbiol. Immunol. 192:187.[Medline]
  8. Alouf, J. E., C. Geoffroy. 1991. The family of the antigenically-related, cholesterol-binding ("sulphydryl-activated") cytolytic toxins. ed. Sourcebook of Bacterial Protein Toxins 147. Academic Press Limited, London.
  9. Gaillard, J. L., P. Berche, J. Mounier, S. Richard, P. Sansonetti. 1987. In vitro model of penetration and intracellular growth of Listeria monocytogenes in the human enterocyte-like cell line Caco-2. Infect. Immun. 55:2822.[Abstract/Free Full Text]
  10. Portnoy, D. A., P. S. Jacks, D. J. Hinrichs. 1988. Role of hemolysin for the intracellular growth of Listeria monocytogenes. J. Exp. Med. 167:1459.[Abstract/Free Full Text]
  11. Guzman, C. A., E. Domann, M. Rohde, D. Bruder, A. Darji, S. Weiss, J. Wehland, T. Chakraborty, K. N. Timmis. 1996. Apoptosis of mouse dendritic cells is triggered by listeriolysin, the major virulence determinant of Listeria monocytogenes. Mol. Microbol. 20:119.[Medline]
  12. Nishibori, T., H. Xiong, I. Kawamura, M. Arakawa, M. Mitsuyama. 1996. Induction of cytokine gene expression by listeriolysin O and roles of macrophages and NK cells. Infect. Immun. 64:3188.[Abstract]
  13. Tang, P., I. Rosenshine, P. Cossart, B. B. Finlay. 1996. Listeriolysin O activates mitogen-activated protein kinase in eucaryotic cells. Infect. Immun 64:2359.[Abstract]
  14. Sibelius, U., F. Rose, T. Chakraborty, A. Darji, J. Wehland, S. Weiss, W. Seeger, F. Grimminger. 1996. Listeriolysin is a potent inducer of the phosphatidylinositol response and lipid mediator generation in human endothelial cells. Infect. Immun 64:674.[Abstract]
  15. Sibelius, U., E. C. Schulz, F. Rose, K. Hattar, T. Jacobs, S. Weiss, T. Chakraborty, W. Seeger, F. Grimminger. 1999. Role of Listeria monocytogenes exotoxins listeriolysin and phosphatidylinositol-specific phospholipase C in activation of human neutrophils. Infect. Immun. 67:1125.[Abstract/Free Full Text]
  16. Coconnier, M. H., E. Dlissi, M. Robard, C. L. Laboisse, J. L. Gaillard, A. L. Servin. 1998. Listeria monocytogenes stimulates mucus exocytosis in cultured human polarized mucosecreting intestinal cells through action of listeriolysin O. Infect. Immun. 66:3673.[Abstract/Free Full Text]
  17. Kayal, S., A. Lilienbaum, C. Poyart, S. Memet, A. Israel, P. Berche. 1999. Listeriolysin O-dependent activation of endothelial cells during infection with Listeria monocytogenes: activation of NF-{kappa}B and up-regulation of adhesion molecules and chemokines. Mol. Microbiol. 31:1709.[Medline]
  18. Merrick, J. C., B. T. Edelson, V. Bhardway, P. E. Swanson, E. R. Unanue. 1997. Lymphocyte apoptosis during early phase of Listeria infection in mice. Am. J. Pathol. 151:185.
  19. Nato, F., K. Reich, S. Lhopital, S. Rouyre, C. Geoffroy, J. C. Mazie, P. Cossart. 1991. Production and characterization of neutralizing and nonneutralizing monoclonal antibodies against listeriolysin O. Infect. Immun. 59:4641.[Abstract/Free Full Text]
  20. Bhardwaj, V., O. Kanagawa, P. E. Swanson, E. R. Unanue. 1998. Chronic Listeria infection in SCID mice: requirement for the carrier state and the dual role of T cells in transferring protection or suppression. J. Immunol. 160:376.[Abstract/Free Full Text]
  21. Osebold, J. W., M. T. Sawyer. 1957. Immunization studies on listeriosis in mice. J. Immunol. 78:262.
  22. Cheers, C., M. Ho. 1983. Resistance and susceptibility of mice to bacterial infection. IV. Functional specificity in natural resistance to facultative intracellular bacteria. J. Reticuloendothel. Soc. 34:299.[Medline]
  23. Casadevall, A.. 1998. Antibody-mediated protection against intracellular pathogens. Trends Microbiol. 6:102.[Medline]
  24. Hage-Chahine, C. M., G. Del Giudice, P. H. Lambert, J. C. Pechere. 1992. Hemolysin-producing Listeria monocytogenes affects the immune response to T-cell-dependent and T-cell-independent antigens. Infect. Immun. 60:1415.[Abstract/Free Full Text]
  25. Safley, S. A., C. W. Cluff, N. E. Marshall, H. K. Ziegler. 1991. Role of listeriolysin-O (LLO) in the T lymphocyte response to infection with Listeria monocytogenes. Identification of T cell epitopes of LLO. J. Immunol. 146:3604.[Abstract]
  26. Harty, J. T., M. J. Bevan. 1992. CD8+ T cells specific for a single nonamer epitope of Listeria monocytogenes are protective in vivo. J. Exp. Med. 175:1531.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 J. Immunol.Home page
J. A. Carrero, H. Vivanco-Cid, and E. R. Unanue
Granzymes Drive a Rapid Listeriolysin O-Induced T Cell Apoptosis
J. Immunol., July 15, 2008; 181(2): 1365 - 1374.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
G. Zhang, K. E. Russell-Lodrigue, M. Andoh, Y. Zhang, L. R. Hendrix, and J. E. Samuel
Mechanisms of Vaccine-Induced Protective Immunity against Coxiella burnetii Infection in BALB/c Mice
J. Immunol., December 15, 2007; 179(12): 8372 - 8380.
[Abstract] [Full Text] [PDF]

Home page
 J Med MicrobiolHome page
W. L. Yu, H. Dan, and M. Lin
Novel protein targets of the humoral immune response to Listeria monocytogenes infection in rabbits
J. Med. Microbiol., July 1, 2007; 56(7): 888 - 895.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
E. Yager, C. Bitsaktsis, B. Nandi, J. W. McBride, and G. Winslow
Essential Role for Humoral Immunity during Ehrlichia Infection in Immunocompetent Mice
Infect. Immun., December 1, 2005; 73(12): 8009 - 8016.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. G. Morrison and R. P. Morrison
A Predominant Role for Antibody in Acquired Immunity to Chlamydial Genital Tract Reinfection
J. Immunol., December 1, 2005; 175(11): 7536 - 7542.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Ravindran, J. Foley, T. Stoklasek, L. H. Glimcher, and S. J. McSorley
Expression of T-bet by CD4 T Cells Is Essential for Resistance to Salmonella Infection
J. Immunol., October 1, 2005; 175(7): 4603 - 4610.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
J. Rivera, O. Zaragoza, and A. Casadevall
Antibody-Mediated Protection against Cryptococcus neoformans Pulmonary Infection Is Dependent on B Cells
Infect. Immun., February 1, 2005; 73(2): 1141 - 1150.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
J. A. Carrero, B. Calderon, and E. R. Unanue
Type I Interferon Sensitizes Lymphocytes to Apoptosis and Reduces Resistance to Listeria Infection
J. Exp. Med., August 16, 2004; 200(4): 535 - 540.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
M. L. Levin, D. J. Coble, and D. E. Ross
Reinfection with Anaplasma phagocytophilum in BALB/c Mice and Cross-Protection between Two Sympatric Isolates
Infect. Immun., August 1, 2004; 72(8): 4723 - 4730.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. A. Carrero, B. Calderon, and E. R. Unanue
Listeriolysin O from Listeria monocytogenes Is a Lymphocyte Apoptogenic Molecule
J. Immunol., April 15, 2004; 172(8): 4866 - 4874.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
H.-M. Feng, T. Whitworth, J. P. Olano, V. L. Popov, and D. H. Walker
Fc-Dependent Polyclonal Antibodies and Antibodies to Outer Membrane Proteins A and B, but Not to Lipopolysaccharide, Protect SCID Mice against Fatal Rickettsia conorii Infection
Infect. Immun., April 1, 2004; 72(4): 2222 - 2228.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
A. Casadevall
Antibody-Mediated Immunity against Intracellular Pathogens: Two-Dimensional Thinking Comes Full Circle
Infect. Immun., August 1, 2003; 71(8): 4225 - 4228.
[Full Text] [PDF]

Home page
 Infect. Immun.Home page
J. S.-y. Li and G. M. Winslow
Survival, Replication, and Antibody Susceptibility of Ehrlichia chaffeensis outside of Host Cells
Infect. Immun., August 1, 2003; 71(8): 4229 - 4237.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
J. C. Sun and M. J. Bevan
Defective CD8 T Cell Memory Following Acute Infection Without CD4 T Cell Help
Science, April 11, 2003; 300(5617): 339 - 342.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Shen, J. K. Whitmire, X. Fan, D. J. Shedlock, S. M. Kaech, and R. Ahmed
A Specific Role for B Cells in the Generation of CD8 T Cell Memory by Recombinant Listeria monocytogenes
J. Immunol., February 1, 2003; 170(3): 1443 - 1451.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
T. Hertzig, M. Weber, L. Greiffenberg, B. S. Holthausen, W. Goebel, K. S. Kim, and M. Kuhn
Antibodies Present in Normal Human Serum Inhibit Invasion of Human Brain Microvascular Endothelial Cells by Listeria monocytogenes
Infect. Immun., January 1, 2003; 71(1): 95 - 100.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
M. Mizuki, A. Nakane, K. Sekikawa, Y.-i. Tagawa, and Y. Iwakura
Comparison of Host Resistance to Primary and Secondary Listeria monocytogenes Infections in Mice by Intranasal and Intravenous Routes
Infect. Immun., September 1, 2002; 70(9): 4805 - 4811.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. S.-y. Li, F. Chu, A. Reilly, and G. M. Winslow
Antibodies Highly Effective in SCID Mice During Infection by the Intracellular Bacterium Ehrlichia chaffeensis Are of Picomolar Affinity and Exhibit Preferential Epitope and Isotype Utilization
J. Immunol., August 1, 2002; 169(3): 1419 - 1425.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
H. Angelakopoulos, K. Loock, D. M. Sisul, E. R. Jensen, J. F. Miller, and E. L. Hohmann
Safety and Shedding of an Attenuated Strain of Listeria monocytogenes with a Deletion of actA/plcB in Adult Volunteers: a Dose Escalation Study of Oral Inoculation
Infect. Immun., July 1, 2002; 70(7): 3592 - 3601.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Rivera, J. Mukherjee, L. M. Weiss, and A. Casadevall
Antibody Efficacy in Murine Pulmonary Cryptococcus neoformans Infection: A Role for Nitric Oxide
J. Immunol., April 1, 2002; 168(7): 3419 - 3427.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
G. Lauvau, S. Vijh, P. Kong, T. Horng, K. Kerksiek, N. Serbina, R. A. Tuma, and E. G. Pamer
Priming of Memory But Not Effector CD8 T Cells by a Killed Bacterial Vaccine
Science, November 23, 2001; 294(5547): 1735 - 1739.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
M. Manohar, D. O. Baumann, N. A. Bos, and J. J. Cebra
Gut Colonization of Mice with actA-Negative Mutant of Listeria monocytogenes Can Stimulate a Humoral Mucosal Immune Response
Infect. Immun., June 1, 2001; 69(6): 3542 - 3549.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
S. G. Morrison and R. P. Morrison
Resolution of Secondary Chlamydia trachomatis Genital Tract Infection in Immune Mice with Depletion of Both CD4+ and CD8+ T cells
Infect. Immun., April 1, 2001; 69(4): 2643 - 2649.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
I. Guleria and J. W. Pollard
Aberrant Macrophage and Neutrophil Population Dynamics and Impaired Th1 Response to Listeria monocytogenes in Colony-Stimulating Factor 1-Deficient Mice
Infect. Immun., March 1, 2001; 69(3): 1795 - 1807.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Pope, S.-K. Kim, A. Marzo, K. Williams, J. Jiang, H. Shen, and L. Lefrancois
Organ-Specific Regulation of the CD8 T Cell Response to Listeria monocytogenes Infection
J. Immunol., March 1, 2001; 166(5): 3402 - 3409.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
Y. Jin, L. Dons, K. Kristensson, and M. E. Rottenberg
Neural Route of Cerebral Listeria monocytogenes Murine Infection: Role of Immune Response Mechanisms in Controling Bacterial Neuroinvasion
Infect. Immun., February 1, 2001; 69(2): 1093 - 1100.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Shu-yi Li, E. Yager, M. Reilly, C. Freeman, G. R. Reddy, A. A. Reilly, F. K. Chu, and G. M. Winslow
Outer Membrane Protein-Specific Monoclonal Antibodies Protect SCID Mice from Fatal Infection by the Obligate Intracellular Bacterial Pathogen Ehrlichia chaffeensis
J. Immunol., February 1, 2001; 166(3): 1855 - 1862.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Mercado, S. Vijh, S. E. Allen, K. Kerksiek, I. M. Pilip, and E. G. Pamer
Early Programming of T Cell Populations Responding to Bacterial Infection
J. Immunol., December 15, 2000; 165(12): 6833 - 6839.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
S. G. Morrison, H. Su, H. D. Caldwell, and R. P. Morrison
Immunity to Murine Chlamydia trachomatis Genital Tract Reinfection Involves B Cells and CD4+ T Cells but Not CD8+ T Cells
Infect. Immun., December 1, 2000; 68(12): 6979 - 6987.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Edelson, B. T.
Right arrow Articles by Unanue, E. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Edelson, B. T.
Right arrow Articles by Unanue, E. R.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS