Induction of Intestinal Th17 Cells by Flagellins From Segmented Filamentous Bacteria.

Yanling Wang,Xin Wang,Yongjia Zhao,Charlie Xiang,Huahai Chen,Xin Chen,Yichen Wu,Yifei Li,Yeshi Yin

doi:10.3389/fimmu.2019.02750

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.

Highlights

The gastrointestinal tract of vertebrates is colonized by a diverse array of microorganisms, that maintain a mutually beneficial relationship with the host [1]
A variety of experimental methods were used to prove that segmented filamentous bacteria (SFB) flagellins can significantly induce mucosal expression of Th17-related cytokines, such as IL-17 and IL-22
In this study, we found that similar to the immunization of mice with salFliC, mice immunized with SFB flagellins promote the swift, intense, transient production of the factors controlling Th17 differentiation and Th17-related cytokines, such as IL-17A, IL17F, and IL-22

Summary

Introduction

The gastrointestinal tract of vertebrates is colonized by a diverse array of microorganisms, that maintain a mutually beneficial relationship with the host [1]. The important link of this relationship is based on the perception of specific bacterial species, that trigger responses required for maintaining homeostasis between microbiota and host [2] It is well-recognized that several individual bacterial species can affect the development and function of various immune cells. SFBs are spore-forming gram-positive bacteria with a segmented and filamentous morphology and primarily colonize the distal ileum of mice and rats [7]. These bacteria tightly adhere to small intestinal epithelial cells (SI ECs), influencing the immune responses [5, 8]. Cytokine IL-23 is not sufficient to generate Th17, but maintains the expansion and pathogenicity of Th17 cells [14]

Methods

Results

Conclusion