Back to Search
Start Over
Type I Interferons Suppress Anti-parasitic Immunity and Can Be Targeted to Improve Treatment of Visceral Leishmaniasis.
- Source :
-
Cell reports [Cell Rep] 2020 Feb 25; Vol. 30 (8), pp. 2512-2525.e9. - Publication Year :
- 2020
-
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 <superscript>+</superscript> 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 <superscript>+</superscript> 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 <superscript>+</superscript> 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.<br />Competing Interests: Declaration of Interests S.W.L. has served on an advisory board for Novartis, the owner of Jakavi (ruxolitinib), a drug used in this study.<br /> (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Amphotericin B pharmacology
Animals
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes immunology
Cytokines metabolism
Dendritic Cells drug effects
Dendritic Cells immunology
Epitopes
Humans
Inflammation immunology
Inflammation pathology
Interferon-gamma pharmacology
Mice, Inbred C57BL
Nitriles
Parasites drug effects
Pyrazoles pharmacology
Pyrimidines
Receptor, Interferon alpha-beta deficiency
Receptor, Interferon alpha-beta metabolism
Signal Transduction drug effects
Immunity drug effects
Interferon Type I pharmacology
Leishmaniasis, Visceral immunology
Leishmaniasis, Visceral parasitology
Parasites immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 30
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 32101732
- Full Text :
- https://doi.org/10.1016/j.celrep.2020.01.099