| Literature DB >> 32101732 |
Rajiv Kumar1, Patrick T Bunn2, Siddharth Sankar Singh3, Susanna S Ng4, Marcela Montes de Oca5, Fabian De Labastida Rivera5, Shashi Bhushan Chauhan3, Neetu Singh3, Rebecca J Faleiro5, Chelsea L Edwards6, Teija C M Frame5, Meru Sheel7, Rebecca J Austin5, Steven W Lane5, Tobias Bald5, Mark J Smyth5, Geoffrey R Hill8, Shannon E Best5, Ashraful Haque5, Dillon Corvino5, Nic Waddell5, Lambross Koufariotis5, Pamela Mukhopadhay5, Madhukar Rai3, Jaya Chakravarty3, Om Prakash Singh3, David Sacks9, Susanne Nylen10, Jude Uzonna11, Shyam Sundar3, Christian R Engwerda12.
Abstract
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.Entities:
Keywords: CD4(+) T cells; type I interferons; visceral leishmaniasis
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Year: 2020 PMID： 32101732 PMCID： PMC7981274 DOI： 10.1016/j.celrep.2020.01.099
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423