| First Author | Kumar R | Year | 2020 |
| Journal | Cell Rep | Volume | 30 |
| Issue | 8 | Pages | 2512-2525.e9 |
| PubMed ID | 32101732 | Mgi Jnum | J:288067 |
| Mgi Id | MGI:6416018 | Doi | 10.1016/j.celrep.2020.01.099 |
| Citation | Kumar R, et al. (2020) Type I Interferons Suppress Anti-parasitic Immunity and Can Be Targeted to Improve Treatment of Visceral Leishmaniasis. Cell Rep 30(8):2512-2525.e9 |
| abstractText | 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 IFNgamma 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. |
