AUTHOR=Lee Arim , Kim Myun Soo , Cho Daeho , Jang Kyung Ku , Choi Sang Ho , Kim Tae Sung 

TITLE=Vibrio vulnificus RtxA Is a Major Factor Driving Inflammatory T Helper Type 17 Cell Responses in vitro and in vivo

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02095

DOI=10.3389/fimmu.2018.02095

ISSN=1664-3224

ABSTRACT=<p>T helper type 17 (Th17) cells are a subset of pro-inflammatory T helper cells that mediate host defense and pathological inflammation. We have previously reported that host dendritic cells (DCs) infected with <italic>Vibrio vulnificus</italic> induce Th17 responses through the production of several pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6. <italic>V. vulnificus</italic> produces RTX toxin (RtxA), an important virulence factor that determines successful pathophysiology. In this study, we investigated the involvement of RtxA from <italic>V. vulnificus</italic> in Th17 cell induction through the activation and maturation of DCs. The increased expression of the DC surface marker CD40 caused by <italic>V. vulnificus</italic> wild-type infection was reduced by <italic>rtxA</italic> gene mutation in <italic>V. vulnificus</italic>. The mRNA and protein levels of Th17 polarization-related cytokines also decreased in <italic>V. vulnificus rtxA</italic> mutant-infected DCs. In addition, the co-culture of Th cells and DCs infected with <italic>rtxA</italic> mutant <italic>V. vulnificus</italic> resulted in reduction in DC-mediated Th17 responses. Th17 cell responses in the small intestinal lamina propria decreased in mice inoculated with <italic>V. vulnificus rtxA</italic> mutant as compared to those inoculated with the wild-type strain. These decreases in DC maturation, Th17-polarizing cytokine secretion, and Th17 responses attributed to <italic>rtxA</italic> mutation were restored following infection with the <italic>rtxA</italic> revertant strain. Furthermore, the mutation in the <italic>hlyU</italic> gene encoding the activator of <italic>rtxA1</italic> gene reproduced the results observed with <italic>rtxA</italic> mutation. Taken together, <italic>V. vulnificus</italic>, by means of RtxA, induces inflammatory Th17 responses, which may be associated with adaptive responses of the host against <italic>V. vulnificus</italic> infection.</p>