UT Microbiome Consortium, Department of Physiology & Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
Gut Microbes. 2023 Jan-Dec;15(1):2185031. doi: 10.1080/19490976.2023.2185031.
Intestinal contents comprise the largest repository of immunogenic ligands of microbial origin. We undertook this study to assess the predominant microbe-associated molecular patterns (MAMPs) present therein and the receptors) that mediate the innate immune responses to them. Here, we demonstrated that intestinal contents from conventional, but not germ-free, mice and rats triggered robust innate immune responses and . Such immune responses were abrogated in the absence of either myeloid differentiation factor 88 (MyD88) or Toll-like receptor (TLR) 5, but not TLR4, suggesting that the stimuli was flagellin (., protein subunit of flagella that drives bacterial motility). Accordingly, pre-treating intestinal extracts with proteinase, thereby degrading flagellin, was sufficient to block their ability to activate innate immune responses. Taken together, this work serves to underscore flagellin as a major, heat-stable and bioactive MAMP in the intestinal content that confers this milieu strong potential to trigger innate immune responses.
肠道内容物包含最大数量的微生物来源的免疫原性配体库。我们进行这项研究是为了评估其中存在的主要微生物相关分子模式（MAMPs）和介导对它们的先天免疫反应的受体。在这里，我们证明了来自常规而非无菌的小鼠和大鼠的肠道内容物可引发强烈的先天免疫反应。在缺乏髓样分化因子 88 (MyD88)或 Toll 样受体 (TLR) 5 的情况下，这种免疫反应被阻断，但 TLR4 没有，这表明刺激物是鞭毛蛋白（flagellin，驱动细菌运动的鞭毛的蛋白亚基）。因此，用蛋白酶预先处理肠道提取物，从而降解鞭毛蛋白，足以阻止其激活先天免疫反应的能力。总之，这项工作强调了鞭毛蛋白作为肠道内容物中主要的热稳定和生物活性 MAMP，使这种环境具有强烈的潜在触发先天免疫反应的能力。
