Gut microbiota regulates intestinal goblet cell response and mucin production by influencing the TLR2-SPDEF axis in an enteric parasitic infection.
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abstract
Alterations in goblet cell biology constitute one of the most effective host responses against enteric parasites. In the gastrointestinal (GI) tract, millions of bacteria influence these goblet cell responses by binding to pattern recognition receptors such as toll-like receptors (TLRs). Studies suggest that the gut microbiota also interacts bidirectionally with enteric parasites, including Trichuris muris. Here, we study the roles of T. muris-altered microbiota and the TLR2-SPDEF axis in parasitic host defense. In acute T. muris infection, we observed altered gut microbiota composition, which, when transferred to germ-free mice, resulted in increased goblet cell numbers, Th2 cytokines and Muc2 expression, as well as increased Tlr2. Further, antibiotic (ABX)-treated TLR2-/- mice, despite having received the same T. muris-altered microbiota, displayed diminished Th2 response, Muc2 expression, and, intriguingly, diminished SPDEF expression compared to wildtype counterparts. When infected with T. muris, SPDEF-/- mice exhibited a reduced Th2 response and altered microbial composition compared to SPDEF+/+, particularly on day 14 post-infection, and this microbiota was sufficient to alter host goblet cell response when transferred to ABX-treated mice. Taken together, our findings suggest the TLR2-SPDEF axis, via T. muris-induced microbial changes, is an important regulator of goblet cell function and host's parasitic defense.
