Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria.
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 approach...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-10-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC5061386?pdf=render |
| _version_ | 1818196375234412544 |
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| author | Ryan A Zander Jenna J Guthmiller Amy C Graham Rosemary L Pope Bradly E Burke Daniel J J Carr Noah S Butler |
| author_facet | Ryan A Zander Jenna J Guthmiller Amy C Graham Rosemary L Pope Bradly E Burke Daniel J J Carr Noah S Butler |
| author_sort | Ryan A Zander |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T01:33:05Z |
| format | Article |
| id | doaj.art-4585d5bb64b94ec8ac641cfd366f0297 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-12T01:33:05Z |
| publishDate | 2016-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-4585d5bb64b94ec8ac641cfd366f02972022-12-22T00:42:55ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-10-011210e100594510.1371/journal.ppat.1005945Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria.Ryan A ZanderJenna J GuthmillerAmy C GrahamRosemary L PopeBradly E BurkeDaniel J J CarrNoah S ButlerCD4 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.http://europepmc.org/articles/PMC5061386?pdf=render |
| spellingShingle | Ryan A Zander Jenna J Guthmiller Amy C Graham Rosemary L Pope Bradly E Burke Daniel J J Carr Noah S Butler Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria. PLoS Pathogens |
| title | Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria. |
| title_full | Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria. |
| title_fullStr | Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria. |
| title_full_unstemmed | Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria. |
| title_short | Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria. |
| title_sort | type i interferons induce t regulatory 1 responses and restrict humoral immunity during experimental malaria |
| url | http://europepmc.org/articles/PMC5061386?pdf=render |
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