Journal article
Ly6C(hi) inflammatory monocytes promote susceptibility to Leishmania donovani infection
Scientific reports, Vol.7, 14693
10/31/2017
DOI: 10.1038/s41598-017-14935-3
PMCID: PMC5665970
PMID: 29089636
Abstract
Ly6C(hi) inflammatory monocytes (iMO) are critical for host defense against toxoplasmosis and malaria but their role in leishmaniasis is unclear. In this study, we report a detrimental role of Ly6C(hi) iMOs in visceral leishmaniasis (VL) caused by Leishmania donovani. We demonstrate that Ly6C(hi) iMOs are continuously recruited into the spleen and liver during L. donovani infection and they are preferential targets for the parasite. Using microarray- based gene expression profiling, we show that Ly6Chi iMOs isolated from the infected liver and spleen have distinct phenotypic and activation profiles. Furthermore, we demonstrate that blocking the recruitment of Ly6C(hi) iMOs into the liver and spleen during L. donovani infection using a CCR2 antagonist reduces the frequency of the pathogenic IFN-gamma/IL10 dual producer CD4+T cells in the spleen and leads to a significant reduction in parasite loads in the liver and spleen. Using STAT1-/- mice we show that STAT1 is critical for mediating the recruitment of Ly6C(hi) iMOs into organs during L. donovani infection, and adaptive transfer of wild type Ly6C(hi) iMOs into STAT1-/- recipients renders them susceptible to disease. Our findings reveal an unexpected pathogenic role for Ly6C(hi) iMOs in promoting parasite survival in VL and open the possibility of targeting this population for host-directed therapy during VL.
Details
- Title: Subtitle
- Ly6C(hi) inflammatory monocytes promote susceptibility to Leishmania donovani infection
- Creators
- Cesar Terrazas - The Ohio State UniversitySanjay Varikuti - The Ohio State UniversitySteve Oghumu - The Ohio State UniversityHeidi M. Steinkamp - The Ohio State UniversityNurittin Ardic - Başkent UniversityJennifer Kimble - The Ohio State UniversityHira Nakhasi - Center for Biologics Evaluation and ResearchAbhay R. Satoskar - The Ohio State University Wexner Medical Center
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.7, 14693
- DOI
- 10.1038/s41598-017-14935-3
- PMID
- 29089636
- PMCID
- PMC5665970
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- Springer Nature
- Number of pages
- 10
- Grant note
- K01CA207599 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) K01 CA207599 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 10/31/2017
- Academic Unit
- Pediatric Dentistry
- Record Identifier
- 9984367719602771
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