Induction of Intestinal Th17 Cells by Flagellins From Segmented Filamentous Bacteria

Abstract

T-helper-17 (Th17) cells are a subset of CD4+ T cells that can produce the cytokine interleukin (IL)-17 and play vital roles in protecting the host from bacterial and fungal infections, especially at the mucosal surface. These are abundant in the small intestinal lamina propria (SILP) and their differentiation are associated with the colonization of the intestinal flora. Segmented filamentous bacteria (SFB) drew the attention of researchers due to their unique ability to drive the accumulation of Th17 cells in the SI LP of mice. Recent work has highlighted that SFB used microbial adhesion-triggered endocytosis (MATE) to transfer SFB antigenic proteins into small intestinal epithelial cells (SI ECs) and modulate host immune homeostasis. However, which components of SFB are involved in this immune response process remains unclear. Here, we examined the roles of SFB flagellins in Th17 cells induction using various techniques, including ELISA, ELISPOT, and RNA-seq in vitro and in vivo. The results show that the immune function of SFB flagellins is similar to SFB, i.e., induces the appearance of CD4+ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the SI LP. Furthermore, treatment of mice with SFB flagellins lead to a significant increase in the expression of genes associated with the IL-17 signaling pathway, such as IL-6, IL-1β, TNF-α, IL-17A, IL-17F, and IL-22. In addition, SFB flagellins have an intimate relationship with intestinal epithelial cells, influencing the expression of epithelial cell-specific genes such as Nos2, Duox2, Duoxa2, SAA3, Tat, and Lcn2. Thus, we propose that SFB flagellins play a significant role in the involvement of SFB in the induction of intestinal Th17 cells.

Acceptive Immunity: The Role of Fucosylated Glycans in Human Host–Microbiome Interactions

“…SFB stimulate the formation of lymphoid follicles and tertiary lymphoid tissues in the host, which leads to increased sIgA concentrations and the number and activity of IgA-secreting B cells [ 204 ]. SFB can attach to IECs without damaging them, but with induction of the expression of their nos2 , duoX2 , duoXA2 , saa3 , tat , and lcn2 genes [ 205 ] and rearrangement of the IEC cytoskeleton at the contact site [ 202 ]. SFB induce the appearance of Th17 cells producing IL-17 and IL-22 [ 205 , 206 ].…”

“…SFB can attach to IECs without damaging them, but with induction of the expression of their nos2 , duoX2 , duoXA2 , saa3 , tat , and lcn2 genes [ 205 ] and rearrangement of the IEC cytoskeleton at the contact site [ 202 ]. SFB induce the appearance of Th17 cells producing IL-17 and IL-22 [ 205 , 206 ]. T cell priming and their differentiation into Th17 cells occurs locally in the lamina propria [ 207 ] after the interaction of SFB flagellin with TLR5 CD11c hi CD11b hi DCs.…”

Intraventricular IL-17A administration activates microglia and alters their localization in the mouse embryo cerebral cortex

“…Maternal immune activation (MIA) has been suggested to affect fetal brain development and to cause autism spectrum disorder (ASD) symptoms. Interleukin 17A (IL-17A) is a candidate mediator responsible for MIAinduced ASD pathogenesis [1][2][3][4]. In a commonly used mouse model of MIA, polyinosinic-polycytidylic acid [poly(I:C)], a viral mimic that potently induces inflammation, is administered to pregnant female mice [5,6].…”

Intraventricular IL-17A Administration Activates Microglia and Alters Their Localization in the Mouse Embryo Cerebral Cortex

“…Maternal immune activation (MIA) has been suggested to affect fetal brain development and to cause autism spectrum disorder (ASD) symptoms. Interleukin 17A (IL-17A) is a candidate mediator responsible for MIA-induced ASD pathogenesis [1][2][3][4]. In a commonly used mouse model of MIA, polyinosinic-polycytidylic acid [poly(I:C)], a viral mimic that potently induces inflammation, is administered to pregnant female mice [5,6].…”