1. The protozoan commensal Tritrichomonas musculis is a natural adjuvant for mucosal IgA.
- Author
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Cao, Eric, Burrows, Kyle, Chiaranunt, Pailin, Popovic, Ana, Zhou, Xueyang, Xie, Cong, Thakur, Ayushi, Britton, Graham, Spindler, Matthew, Ngai, Louis, Tai, Siu, Dasoveanu, Dragos, Nguyen, Albert, Faith, Jeremiah, Parkinson, John, Gommerman, Jennifer, and Mortha, Arthur
- Subjects
Animals ,Immunoglobulin A ,Tritrichomonas ,Mice ,Immunity ,Mucosal ,Symbiosis ,Mice ,Inbred C57BL ,Intestinal Mucosa ,B-Lymphocytes ,Plasma Cells ,Adjuvants ,Immunologic ,Germinal Center ,T-Lymphocytes ,Helper-Inducer - Abstract
Immunoglobulin (Ig) A supports mucosal immune homeostasis and host-microbiota interactions. While commensal bacteria are known for their ability to promote IgA, the role of non-bacterial commensal microbes in the induction of IgA remains elusive. Here, we demonstrate that permanent colonization with the protozoan commensal Tritrichomonas musculis (T.mu) promotes T cell-dependent, IgA class-switch recombination, and intestinal accumulation of IgA-secreting plasma cells (PC). T.mu colonization specifically drives the expansion of T follicular helper cells and a unique ICOS+ non-Tfh cell population, accompanied by an increase in germinal center B cells. Blockade of ICOS:ICOSL co-stimulation or MHCII-expression on B cells is central for the induction of IgA following colonization by T.mu, implicating a previously underappreciated mode of IgA induction following protozoan commensal colonization. Finally, T.mu further improves the induction of IgA-secreting PC specific to orally ingested antigens and their peripheral dissemination, identifying T.mu as a natural adjuvant for IgA. Collectively, these findings propose a protozoa-driven mode of IgA induction to support intestinal immune homeostasis.
- Published
- 2024