Ly6Chi inflammatory monocytes promote susceptibility to Leishmania donovani infection. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Terrazas, Cesar; Varikuti, Sanjay; Oghumu, Steve; Steinkamp, Heidi; Ardic, Nurittin; Kimble, Jennifer; Nakhasi, Hira; Satoskar, Abhay
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 10
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-14935-3
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract Ly6Chi 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 Ly6Chi iMOs in visceral leishmaniasis (VL) caused byLeishmania donovani . We demonstrate that Ly6Chi iMOs are continuously recruited into the spleen and liver duringL. 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 Ly6Chi iMOs into the liver and spleen duringL. donovani infection using a CCR2 antagonist reduces the frequency of the pathogenic IFN-γ/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 Ly6Chi iMOs into organs duringL. donovani infection, and adaptive transfer of wild type Ly6Chi iMOs into STAT1−/− recipients renders them susceptible to disease. Our findings reveal an unexpected pathogenic role for Ly6Chi iMOs in promoting parasite survival in VL and open the possibility of targeting this population for host-directed therapy during VL.