Abstract

Control of visceral leishmaniasis (VL) caused by Leishmania donovani requires IFN? production by CD4+ T cells. In VL patients, anti-parasitic CD4+ T cell responses are ineffective for unknown reasons. In this study, we measured the expression of genes associated with various immune functions in these cells from VL patients and compared them to CD4+ T cells from the same patients after drug treatment and from endemic controls. We found reduced GATA3, RORC and FOXP3 gene expression in VL patient CD4+ T cells, associated with reduced Th2, Th17 and FOXP3+ CD4+ T regulatory cell frequencies in VL patient blood. IL-2 was an important upstream regulator of CD4+ T cells from VL patients, and functional studies demonstrated the therapeutic potential of IL-2 for improving anti-parasitic immunity. Together, these results provide new insights into the characteristics of CD4+ T cells from VL patients that can be used to improve anti-parasitic immune responses.

Authors	Chauhan, Shashi Bhushan; Faleiro, Rebecca; Kumar, Rajiv; Ng, Susanna; Singh, Bhawana; Singh, Om Prakash; Singh, Siddharth Sankar; Amante, Fiona; Rivera, Fabian de Labastida; Rai, Madhukar; Chakravarty, Jaya; Sacks, David; Nylen, Susanne; Sundar, Shyam; Engwerda, Christian
Journal	JOURNAL OF INFECTIOUS DISEASES
Pages	163-173
Volume	220
Date	1/02/2019
Grant ID	U19 AI074321
Funding Body	National Institutes of Health Tropical Medicine Research Center
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1093/infdis/jiz074