Journal article
Leishmania major degrades murine CXCL1 - An immune evasion strategy
PLoS neglected tropical diseases, Vol.13(7), p.e0007533
07/2019
DOI: 10.1371/journal.pntd.0007533
PMCID: PMC6625741
PMID: 31260451
Abstract
Leishmaniasis is a global health problem with an estimated report of 2 million new cases every year and more than 1 billion people at risk of contracting this disease in endemic areas. The innate immune system plays a central role in controlling L. major infection by initiating a signaling cascade that results in production of pro-inflammatory cytokines and recruitment of both innate and adaptive immune cells. Upon infection with L. major, CXCL1 is produced locally and plays an important role in the recruitment of neutrophils to the site of infection. Herein, we report that L. major specifically targets murine CXCL1 for degradation. The degradation of CXCL1 is not dependent on host factors as L. major can directly degrade recombinant CXCL1 in a cell-free system. Using mass spectrometry, we discovered that the L. major protease cleaves at the C-terminal end of murine CXCL1. Finally, our data suggest that L. major metalloproteases are involved in the direct cleavage and degradation of CXCL1, and a synthetic peptide spanning the CXCL1 cleavage site can be used to inhibit L. major metalloprotease activity. In conclusion, our study has identified an immune evasion strategy employed by L. major to evade innate immune responses in mice, likely reservoirs in the endemic areas, and further highlights that targeting these L. major metalloproteases may be important in controlling infection within the reservoir population and transmittance of the disease.
Details
- Title: Subtitle
- Leishmania major degrades murine CXCL1 - An immune evasion strategy
- Creators
- Matthew S Yorek - Department of Internal Medicine, University of Iowa, Iowa City, IA, United States of AmericaBarun Poudel - Department of Internal Medicine, University of Iowa, Iowa City, IA, United States of AmericaLalita Mazgaeen - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA, United States of AmericaR Marshall Pope - The Proteomics Facility, University of Iowa, Iowa City, IA, United States of AmericaMary E Wilson - Iowa City VA Medical Center, Iowa City, IA, United States of AmericaPrajwal Gurung - Immunology Graduate Program, University of Iowa, Iowa City, IA, United States of America
- Resource Type
- Journal article
- Publication Details
- PLoS neglected tropical diseases, Vol.13(7), p.e0007533
- DOI
- 10.1371/journal.pntd.0007533
- PMID
- 31260451
- PMCID
- PMC6625741
- NLM abbreviation
- PLoS Negl Trop Dis
- ISSN
- 1935-2727
- eISSN
- 1935-2735
- Publisher
- United States
- Grant note
- R21 AI088177 / NIAID NIH HHS\nP30 ES005605 / NIEHS NIH HHS\nK22 AI127836 / NIAID NIH HHS\nHoward Hughes Medical Institute
- Language
- English
- Date published
- 07/2019
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; International Programs; Stead Family Department of Pediatrics; Epidemiology; Medicine Administration; Internal Medicine
- Record Identifier
- 9984001200502771
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