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
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • 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
  • Log in

Search

  • Advanced search
The Journal of Immunology
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons
  • Subscribe
  • Log in
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
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • 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

In This Issue

J Immunol August 1, 2014, 193 (3) 973-974; DOI: https://doi.org/10.4049/jimmunol.1490026
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

IRF10: A Cold Shower for Fish IFN

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

IFN regulatory factor (IRF) 10 is an IRF family member that is expressed solely in birds and fish. Many IRFs, including IRF1, 3, and 7, play an integral role in positively regulating the IFN response, a first line of immune defense against viral invasion, but whether IRF10 is involved in this process in fish is unclear. To elucidate whether IRF10 contributes to IFN response regulation, Li et al. (p. 1100) characterized the expression and mechanism of action of IRF10 in the context of antiviral immune responses in Danio rerio zebrafish. They found that IRF10 was induced in parallel with IFN-stimulated genes in zebrafish embryo fibroblast-like (ZF4) cells upon polyinosinic:polycytidylic acid (poly I:C) stimulation, suggesting that IRF10 is likely a typical IFN-stimulated gene. However, in stark contrast to most IRFs, in epithelioma papulosum cyprinid (EPC) cells stimulated with poly I:C, D. rerio IRF10 (DrIRF10) inhibited the promoter activation of DrIFN1 and DrIFN3, genes that positively regulate IFN signaling. Functional domain analysis of DrIRF10 revealed that this inhibition could be mediated through either the DNA-binding or the IRF association domain. In EPC cells infected with spring viremia of carp virus, a single-stranded RNA virus, overexpression of DrIRF10 decreased the transcription of IFN-stimulated genes, including DrIFN1, RIG-I, and Vig-1 and increased the susceptibility of host cells to viral infection. Together, these data define a unique negative regulatory function for DrIRF10 in dampening inflammatory IFN responses in fish.

Gut Microbiota Birth Immunoregulation

Microbial colonization of the sterile gastrointestinal tract in newborns profoundly impacts the development of immunity and immune tolerance, and factors including mode of birth delivery and the environment can influence gut microbiota composition in early life. To determine the relative contribution of these variables to gastrointestinal tract colonization, Hansen et al. (p. 1213) analyzed the gut microbiota composition of mice delivered via Cesarian section (C-section) and cross-fostered to genetically unrelated or identical strains. Fecal gut microbiota of mice delivered via C-section resembled that of the foster strain, indicating that the environment altered gut microbiota composition in young mice. To separate the influence of environment versus delivery mode, the authors compared the gut microbiota of NOD mice delivered vaginally or via C-section and fostered to NOD females with similar gut microbiota compositions. Mice born via C-section rather than vaginal delivery had increased abundance of Bacteriodes genus and Lachnospiraceae family microbes and lower Rikenellaceae and Ruminococcus abundance. Differences in gut microbiota composition between vaginally and C-section delivered mice became less evident as mice aged; however, adult mice delivered via C-section had lower proportions of Foxp3+ regulatory T cells, tolerogenic CD103+ dendritic cells, and Il10 gene expression in mesenteric lymph nodes and spleen. Delivery mode did not affect type-1 diabetes incidence or insulitis in adult NOD mice. These data indicate that mode of delivery influences colonization of the gastrointestinal tract, which has long term effects on the development and function of immunoregulatory immune responses.

Carg5 Controls Candida

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Invasive infections with the fungal pathogen Candida albicans in healthy individuals are uncommon and thought to be associated with a genetic predisposition toward susceptibility to this pathogen. The complement system plays a critical role in early defense against fungal pathogens and triggers the recruitment of inflammatory myeloid cells and the production of reactive oxygen species (ROS). In mice, susceptibility to infection is associated with a 2-bp deletion in the C5 gene, which causes C5 deficiency. Using SM/J mice, which are C5-sufficient but susceptible to C. albicans infection, Radovanovic et al. (p. 1290) identified Carg5 as a novel locus on chromosome 15 that regulates susceptibility to C. albicans infection and fungal proliferation in a C5-independent manner. C. albicans infection induced a strong recruitment of CD11b+Ly6G+ neutrophils to the blood and spleen of both SM/J and control mice; however, neutrophils from SM/J mice had lower surface expression of Ly6G compared with control mice. A significant effect of Carg5 allele copy number on Ly6G expression was observed using SM/J and control mice that were homozygous or heterozygous at Carg5. Ly6G expression was also found to be inversely correlated to fungal burden. Additionally, SM/J mouse neutrophils and macrophages produced less ROS relative to cells from control mice. Fungal burden in SM/J mice was associated with elevated serum CCL2, a chemokine involved in inflammatory monocyte trafficking. In this study, the authors identify Carg5, a novel C5-independent locus, which regulates both Ly6G expression and C. albicans susceptibility.

Immunoproteasome Governs Transcription

Immunoproteasomes (IPs) perform proteolysis of cellular proteins integral to the generation of MHC-I–associated peptides, but their regulatory functions in other immune and nonimmune cell processes are not well understood. Verteuil et al. (p. 1121) hypothesized that IPs may have nonredundant effects on cellular gene expression in both immune and nonimmune signaling pathways. To test this, they used multidimensional profiling of bone marrow–derived wild-type (WT) and Lmp7 and Mecl1 double knockout (dKO) dendritic cells (DCs), which lack integral IP signaling components, and found that IPs regulate expression of 226 gene transcripts at different developmental stages in a cell-autonomous manner. To determine the global influence of IPs on the transcriptional program and biology of DCs, the authors performed RNA-sequencing analyses at sequential time points during in vitro LPS-induced WT and dKO DC maturation and found 8104 differentially expressed transcripts. Many of these transcripts affected the regulation of signaling pathway genes such as IRFs, NF-κB, and STATs. Gene ontology–term enrichment analyses on several gene clusters also confirmed that IP defects altered expression of housekeeping genes and genes involved in immune- and inflammation-related biological processes. To determine if these transcriptional variations translated to functional differences in WT and dKO DCs, these cells were compared in T cell priming assays in vitro, wherein dKO DCs mediated defective primary and secondary T cell priming. These data demonstrate that IPs are vital to transcriptional regulation of DC genes and shed light on IP involvement in processes beyond the generation of MHC-I–associated peptides.

Protection against Parasites

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Whole parasite immunizations provide protection against malaria and prevent symptoms of parasitic blood stage (BS) infection; however, the alternative infection–treatment–vaccination (ITV) strategy involving immunization with wild-type (WT) sporozoites under drug coverage requires fewer sporozoites to elicit protection. Malarial resistance to chloroquine (CQ) has promoted the use of artesunate (AS)-ITV as a defense strategy against malaria. Because CQ results in the persistence of, whereas AS eliminates, BS parasites, Peng et al. (p. 1268) sought to understand the different immune responses elicited by immunization with whole Plasmodium in the presence or absence of BS parasites. In mice, three immunization courses of CQ- or AS-ITV combined with WT P. yoelii infection conferred sterile protection against the pre-erythrocytic stage of the malaria parasite. However, protection against BS parasites was only observed with CQ-ITV, not AS-ITV, following immunization and i.v. challenge with malaria-infected RBCs. Both CQ- and AS-ITV strategies in mice induced circumsporozoite protein–specific CD8+ T effector memory cells in the liver that inhibited liver stage parasite development when cocultured with primary hepatocytes infected with P. yoelii sporozoites. Additionally, CQ- and AS-ITV led to the development of Abs recognizing sporozoite and liver stage parasites, whereas only CQ-ITV induced Abs recognizing BS parasites; however, none of these Abs passively conferred protection in vivo against infection either with sporozoites or malaria-infected RBCs. These results contribute to malarial vaccine design by directly comparing the efficacy of immunization strategies against various forms of the malaria parasite.

  • Copyright © 2014 by The American Association of Immunologists, Inc.
PreviousNext
Back to top

In this issue

The Journal of Immunology: 193 (3)
The Journal of Immunology
Vol. 193, Issue 3
1 Aug 2014
  • 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.
In This Issue
(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.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
In This Issue
The Journal of Immunology August 1, 2014, 193 (3) 973-974; DOI: 10.4049/jimmunol.1490026

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
In This Issue
The Journal of Immunology August 1, 2014, 193 (3) 973-974; DOI: 10.4049/jimmunol.1490026
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • IRF10: A Cold Shower for Fish IFN
    • Gut Microbiota Birth Immunoregulation
    • Carg5 Controls Candida
    • Immunoproteasome Governs Transcription
    • Protection against Parasites
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Top Reads
  • In This Issue
  • In This Issue
Show more IN THIS ISSUE

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
  • FAR 889
  • Privacy Policy
  • Disclaimer

Journal Services

  • Email Alerts
  • RSS Feeds
  • ImmunoCasts
  • Twitter

Copyright © 2022 by The American Association of Immunologists, Inc.

Print ISSN 0022-1767        Online ISSN 1550-6606