Journal article
Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria
PLoS pathogens, Vol.12(10), pp.e1005945-e1005945
10/2016
DOI: 10.1371/journal.ppat.1005945
PMCID: PMC5061386
PMID: 27732671
Abstract
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-γ, 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.
Details
- Title: Subtitle
- Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria
- Creators
- Ryan A Zander - Departments of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of AmericaJenna J Guthmiller - Departments of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of AmericaAmy C Graham - Departments of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of AmericaRosemary L Pope - Departments of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of AmericaBradly E Burke - Departments of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of AmericaDaniel J J Carr - Graduate Program in Biosciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of AmericaNoah S Butler - Graduate Program in Biosciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.12(10), pp.e1005945-e1005945
- DOI
- 10.1371/journal.ppat.1005945
- PMID
- 27732671
- PMCID
- PMC5061386
- NLM abbreviation
- PLoS Pathog
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Publisher
- United States
- Grant note
- K22 AI099070 / NIAID NIH HHS\nR01 AI053108 / NIAID NIH HHS\nT32 AI007633 / NIAID NIH HHS\nR01 AI125446 / NIAID NIH HHS\nP20 GM103447 / NIGMS NIH HHS
- Language
- English
- Date published
- 10/2016
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984001212902771
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