Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Coxiella burnetii blocks intracellular IL-17 signaling in macrophages

Tatiana M. Clemente, Minal Mulye, Anna V. Justis, Srinivas Nallandhighal, Tuan M. Tran, View ORCID ProfileStacey D. Gilk
doi: https://doi.org/10.1101/367920
Tatiana M. Clemente
1Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Minal Mulye
1Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna V. Justis
1Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Srinivas Nallandhighal
2Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States of America.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tuan M. Tran
2Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States of America.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stacey D. Gilk
1Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States of America.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Stacey D. Gilk
  • For correspondence: sgilk@iu.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Coxiella burnetii is an obligate intracellular bacterium and the etiological agent of Q fever. Successful host cell infection requires the Coxiella Type IVB Secretion System (T4BSS), which translocates bacterial effector proteins across the vacuole membrane into the host cytoplasm, where they manipulate a variety of cell processes. To identify host cell targets of Coxiella T4BSS effector proteins, we determined the transcriptome of murine alveolar macrophages infected with a Coxiella T4BSS effector mutant. We identified a set of inflammatory genes that are significantly upregulated in T4BSS mutant-infected cells compared to mock-infected cells or cells infected with wild type (WT) bacteria, suggesting Coxiella T4BSS effector proteins downregulate expression of these genes. In addition, the IL-17 signaling pathway was identified as one of the top pathways affected by the bacteria. While previous studies demonstrated that IL-17 plays a protective role against several pathogens, the role of IL-17 during Coxiella infection is unknown. We found that IL-17 kills intracellular Coxiella in a dose-dependent manner, with the T4BSS mutant exhibiting significantly more sensitivity to IL-17 than WT bacteria. In addition, quantitative PCR confirmed increased expression of IL-17 downstream signaling genes in T4BSS mutant-infected cells compared to WT or mock-infected cells, including the pro-inflammatory cytokines I11a, Il1b and Tnfa, the chemokines Cxcl2 and Ccl5, and the antimicrobial protein Lcn2. We further confirmed that the Coxiella T4BSS downregulates macrophage CXCL2/MIP-2 and CCL5/RANTES protein levels following IL-17 stimulation. Together, these data suggest that Coxiella downregulates IL-17 signaling in a T4BSS-dependent manner in order to escape the macrophage immune response.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted July 12, 2018.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Coxiella burnetii blocks intracellular IL-17 signaling in macrophages
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Coxiella burnetii blocks intracellular IL-17 signaling in macrophages
Tatiana M. Clemente, Minal Mulye, Anna V. Justis, Srinivas Nallandhighal, Tuan M. Tran, Stacey D. Gilk
bioRxiv 367920; doi: https://doi.org/10.1101/367920
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Coxiella burnetii blocks intracellular IL-17 signaling in macrophages
Tatiana M. Clemente, Minal Mulye, Anna V. Justis, Srinivas Nallandhighal, Tuan M. Tran, Stacey D. Gilk
bioRxiv 367920; doi: https://doi.org/10.1101/367920

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4384)
  • Biochemistry (9609)
  • Bioengineering (7103)
  • Bioinformatics (24896)
  • Biophysics (12632)
  • Cancer Biology (9974)
  • Cell Biology (14372)
  • Clinical Trials (138)
  • Developmental Biology (7966)
  • Ecology (12124)
  • Epidemiology (2067)
  • Evolutionary Biology (16002)
  • Genetics (10936)
  • Genomics (14755)
  • Immunology (9880)
  • Microbiology (23697)
  • Molecular Biology (9490)
  • Neuroscience (50924)
  • Paleontology (370)
  • Pathology (1541)
  • Pharmacology and Toxicology (2686)
  • Physiology (4023)
  • Plant Biology (8674)
  • Scientific Communication and Education (1511)
  • Synthetic Biology (2402)
  • Systems Biology (6444)
  • Zoology (1346)