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Leishmania major degrades murine CXCL1 - An immune evasion strategy.

Publication ,  Journal Article
Yorek, MS; Poudel, B; Mazgaeen, L; Pope, RM; Wilson, ME; Gurung, P
Published in: PLoS neglected tropical diseases
July 2019

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.

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Published In

PLoS neglected tropical diseases

DOI

EISSN

1935-2735

ISSN

1935-2727

Publication Date

July 2019

Volume

13

Issue

7

Start / End Page

e0007533

Related Subject Headings

  • Tropical Medicine
  • Signal Transduction
  • Recombinant Proteins
  • Mice
  • Metalloproteases
  • Leishmaniasis
  • Leishmania major
  • Immunity, Innate
  • Immune Evasion
  • Host-Pathogen Interactions
 

Citation

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Yorek, M. S., Poudel, B., Mazgaeen, L., Pope, R. M., Wilson, M. E., & Gurung, P. (2019). Leishmania major degrades murine CXCL1 - An immune evasion strategy. PLoS Neglected Tropical Diseases, 13(7), e0007533. https://doi.org/10.1371/journal.pntd.0007533
Yorek, Matthew S., Barun Poudel, Lalita Mazgaeen, R Marshall Pope, Mary E. Wilson, and Prajwal Gurung. “Leishmania major degrades murine CXCL1 - An immune evasion strategy.PLoS Neglected Tropical Diseases 13, no. 7 (July 2019): e0007533. https://doi.org/10.1371/journal.pntd.0007533.
Yorek MS, Poudel B, Mazgaeen L, Pope RM, Wilson ME, Gurung P. Leishmania major degrades murine CXCL1 - An immune evasion strategy. PLoS neglected tropical diseases. 2019 Jul;13(7):e0007533.
Yorek, Matthew S., et al. “Leishmania major degrades murine CXCL1 - An immune evasion strategy.PLoS Neglected Tropical Diseases, vol. 13, no. 7, July 2019, p. e0007533. Epmc, doi:10.1371/journal.pntd.0007533.
Yorek MS, Poudel B, Mazgaeen L, Pope RM, Wilson ME, Gurung P. Leishmania major degrades murine CXCL1 - An immune evasion strategy. PLoS neglected tropical diseases. 2019 Jul;13(7):e0007533.

Published In

PLoS neglected tropical diseases

DOI

EISSN

1935-2735

ISSN

1935-2727

Publication Date

July 2019

Volume

13

Issue

7

Start / End Page

e0007533

Related Subject Headings

  • Tropical Medicine
  • Signal Transduction
  • Recombinant Proteins
  • Mice
  • Metalloproteases
  • Leishmaniasis
  • Leishmania major
  • Immunity, Innate
  • Immune Evasion
  • Host-Pathogen Interactions