| First Author | Zander RA | Year | 2016 |
| Journal | PLoS Pathog | Volume | 12 |
| Issue | 10 | Pages | e1005945 |
| PubMed ID | 27732671 | Mgi Jnum | J:257721 |
| Mgi Id | MGI:5918223 | Doi | 10.1371/journal.ppat.1005945 |
| Citation | Zander RA, et al. (2016) Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria. PLoS Pathog 12(10):e1005945 |
| abstractText | CD4 T cell-dependent antibody responses are essential for limiting Plasmodium parasite replication and the severity of malaria; however, the factors that regulate humoral immunity during highly inflammatory, Th1-biased systemic infections are poorly understood. Using genetic and biochemical approaches, we show that Plasmodium infection-induced type I interferons limit T follicular helper accumulation and constrain anti-malarial humoral immunity. Mechanistically we show that CD4 T cell-intrinsic type I interferon signaling induces T-bet and Blimp-1 expression, thereby promoting T regulatory 1 responses. We further show that the secreted effector cytokines of T regulatory 1 cells, IL-10 and IFN-gamma, collaborate to restrict T follicular helper accumulation, limit parasite-specific antibody responses, and diminish parasite control. This circuit of interferon-mediated Blimp-1 induction is also operational during chronic virus infection and can occur independently of IL-2 signaling. Thus, type I interferon-mediated induction of Blimp-1 and subsequent expansion of T regulatory 1 cells represent generalizable features of systemic, inflammatory Th1-biased viral and parasitic infections that are associated with suppression of humoral immunity. |
