Ostadmohammadi Soheila, Nojoumi Seyed Ali, Fateh Abolfazl, Siadat Seyed Davar, Sotoodehnejadnematalahi Fattah
1Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
2Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.
Acta Microbiol Immunol Hung. 2022 Apr 7. doi: 10.1556/030.2022.01678.
Gut microbiota can interact with the immune system through direct or indirect pathways. In the indirect pathway, gut microbiota produces metabolites such as short chain fatty acids (SCFAs), which may modulate the immune response. SCFAs reduce inflammation, repair intestinal barrier, and induce propagation of specific immune cells, e.g., T regulatory cells (Treg), which can suppress reactive cells such as macrophage and dendritic cells (DCs). As one of the most dominant members of microbiota, Clostridium produces SCFAs. As one of SCFA members, butyrate plays an important role in the modulation of immune cells. Through butyrate production, Clostridium helps to generate aryl hydrocarbon receptor (AhR). AhR interacts with many proteins inside the cytoplasm including Heat Shock Protein 90 (HSP 90), HSP 23, and chaperone. Activation of AhR leads to its translocation inside the nucleus and gene expression, which yields cell differentiation, energy metabolism, microbial defense, and immune cell propagation. Moreover, it may interact with other cells like B-cell and epithelial cell, which are responsible for modulation and maturation, respectively. AhR causes upregulation in the co-stimulatory marker in the DCs and interacts with nuclear factor KB (NF-ĸB) to modulate cell function. Butyrate induces Treg (iTreg) propagation and upregulates the Forkhead box p3 (FOXP3) as a special marker of Treg cell. It may also yield signaling through G-protein coupled receptors (GPRs) which, in turn, facilitates polymorphonuclear (PMN) chemotaxis.The interaction between microbiota and non-immune cells, such as Paneth cells, leads to the secretion of antimicrobial substance, erection of barriers against bacterial pathogens, and regulation of microbiota composition via feedback effect. In addition, the components released from microbiota, such as peptidoglycan, reinforce the maturation of both the immune system and non-immune tissue development. Moreover, microbiota can directly activate the effector cells, e.g., macrophage, to secrete cytokines and propagate Treg cells.
肠道微生物群可通过直接或间接途径与免疫系统相互作用。在间接途径中，肠道微生物群产生代谢产物，如短链脂肪酸（SCFA），其可能调节免疫反应。短链脂肪酸可减轻炎症、修复肠道屏障并诱导特定免疫细胞（如调节性T细胞（Treg））的增殖，而调节性T细胞可抑制反应性细胞，如巨噬细胞和树突状细胞（DC）。作为微生物群中最主要的成员之一，梭菌可产生短链脂肪酸。作为短链脂肪酸的成员之一，丁酸盐在免疫细胞的调节中发挥重要作用。通过产生丁酸盐，梭菌有助于生成芳烃受体（AhR）。AhR与细胞质内的许多蛋白质相互作用，包括热休克蛋白90（HSP 90）、HSP 23和伴侣蛋白。AhR的激活导致其向细胞核内转运并进行基因表达，从而产生细胞分化、能量代谢、微生物防御和免疫细胞增殖。此外，它可能与其他细胞相互作用，如B细胞和上皮细胞，它们分别负责调节和成熟。AhR导致树突状细胞中共刺激标志物的上调，并与核因子κB（NF-κB）相互作用以调节细胞功能。丁酸盐诱导调节性T细胞（iTreg）增殖，并上调叉头框p3（FOXP3）作为调节性T细胞的特殊标志物。它还可能通过G蛋白偶联受体（GPR）产生信号，进而促进多形核白细胞（PMN）的趋化作用。微生物群与非免疫细胞（如潘氏细胞）之间的相互作用导致抗菌物质的分泌、对细菌病原体屏障的建立以及通过反馈效应调节微生物群组成。此外，微生物群释放的成分，如肽聚糖，可加强免疫系统的成熟和非免疫组织的发育。此外，微生物群可直接激活效应细胞，如巨噬细胞，以分泌细胞因子并促进调节性T细胞的增殖。
