Yousefi Yeganeh, Haider Zarin, Grondin Jensine A, Wang Huaqing, Haq Sabah, Banskota Suhrid, Seto Tyler, Surette Michael, Khan Waliul I
Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada; Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada.
Mucosal Immunol. 2025 Aug;18(4):810-824. doi: 10.1016/j.mucimm.2025.03.007. Epub 2025 Mar 29.
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.
杯状细胞生物学的改变是宿主对抗肠道寄生虫最有效的反应之一。在胃肠道中，数以百万计的细菌通过与模式识别受体（如Toll样受体，TLRs）结合来影响这些杯状细胞反应。研究表明，肠道微生物群也与包括鼠鞭虫在内的肠道寄生虫进行双向相互作用。在此，我们研究了鼠鞭虫改变的微生物群和TLR2-SPDEF轴在寄生虫宿主防御中的作用。在急性鼠鞭虫感染中，我们观察到肠道微生物群组成发生改变，将其转移到无菌小鼠体内后，导致杯状细胞数量增加、Th2细胞因子和Muc2表达增加，以及Tlr2增加。此外，抗生素（ABX）处理的TLR2小鼠，尽管接受了相同的鼠鞭虫改变的微生物群，但与野生型小鼠相比，其Th2反应、Muc2表达减弱，有趣的是，SPDEF表达也减弱。当感染鼠鞭虫时，与野生型相比，SPDEF小鼠表现出Th2反应降低和微生物组成改变，特别是在感染后第14天，并且当将这种微生物群转移到ABX处理的小鼠体内时，足以改变宿主杯状细胞反应。综上所述，我们的研究结果表明，TLR2-SPDEF轴通过鼠鞭虫诱导的微生物变化，是杯状细胞功能和宿主寄生虫防御的重要调节因子。
