Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria
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Date
2016-10-12Author
Ryan A. Zander
Jenna J. Guthmiller
Amy C. Graham
Rosemary L. Pope
Bradly E. Burke
Daniel J.J. Carr
Noah S. Butler
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Author Summary Humoral immunity is essential for host resistance to pathogens that trigger highly inflammatory immune responses, including Plasmodium parasites, the causative agents of malaria. Long-lived, secreted antibody responses depend on a specialized subset of CD4 T cells called T follicular helper (Tfh) cells. However, anti-Plasmodium humoral immunity is often short-lived, non-sterilizing, and immunity rapidly wanes, leaving individuals susceptible to repeated bouts of malaria. Here we explored the relationship between inflammatory type I interferons, the regulation of pathogen-specific CD4 T cell responses, and humoral immunity using models of experimental malaria and systemic virus infection. We identified that type I interferons promote the formation and accumulation of pathogen-specific CD4 T regulatory 1 cells that co-express interferon-gamma and interleukin-10. Moreover, we show that the combined activity of interferon-gamma and interleukin-10 limits the magnitude of infection-induced Tfh responses, the secretion of parasite-specific secreted antibody, and parasite control. Our study provides new insight into the regulation of T regulatory 1 responses and humoral immunity during inflammatory immune reactions against systemic infections.
Citation
Zander RA, Guthmiller JJ, Graham AC, Pope RL, Burke BE, Carr DJ, et al. (2016) Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria. PLoS Pathog 12(10): e1005945. doi:10.1371/journal.ppat.1005945