학술논문
Type I Interferons Suppress Anti-parasitic Immunity and Can Be Targeted to Improve Treatment of Visceral Leishmaniasis
Document Type
article
Author
Rajiv Kumar; Patrick T. Bunn; Siddharth Sankar Singh; Susanna S. Ng; Marcela Montes de Oca; Fabian De Labastida Rivera; Shashi Bhushan Chauhan; Neetu Singh; Rebecca J. Faleiro; Chelsea L. Edwards; Teija C.M. Frame; Meru Sheel; Rebecca J. Austin; Steven W. Lane; Tobias Bald; Mark J. Smyth; Geoffrey.R. Hill; Shannon E. Best; Ashraful Haque; Dillon Corvino; Nic Waddell; Lambross Koufariotis; Pamela Mukhopadhay; Madhukar Rai; Jaya Chakravarty; Om Prakash Singh; David Sacks; Susanne Nylen; Jude Uzonna; Shyam Sundar; Christian R. Engwerda
Source
Cell Reports, Vol 30, Iss 8, Pp 2512-2525.e9 (2020)
Subject
Language
English
ISSN
2211-1247
Abstract
Summary: Type I interferons (IFNs) play critical roles in anti-viral and anti-tumor immunity. However, they also suppress protective immune responses in some infectious diseases. Here, we identify type I IFNs as major upstream regulators of CD4+ T cells from visceral leishmaniasis (VL) patients. Furthermore, we report that mice deficient in type I IFN signaling have significantly improved control of Leishmania donovani, a causative agent of human VL, associated with enhanced IFNγ but reduced IL-10 production by parasite-specific CD4+ T cells. Importantly, we identify a small-molecule inhibitor that can be used to block type I IFN signaling during established infection and acts synergistically with conventional anti-parasitic drugs to improve parasite clearance and enhance anti-parasitic CD4+ T cell responses in mice and humans. Thus, manipulation of type I IFN signaling is a promising strategy for improving disease outcome in VL patients. : CD4+ T cells are critical for control of intracellular parasites such as Leishmania donovani. Kumar et al. show that type I interferons (IFNs) suppress Th1 cells and promote IL-10-producing CD4+ T cells during visceral leishmaniasis (VL). Thus, manipulation of type I IFN signaling may improve disease outcome in VL patients. Keywords: type I interferons, visceral leishmaniasis, CD4+ T cells