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 Vibrio vulnificus induce Th17 responses through the production of several pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6. V. Vulnificus produces RTX toxin (RtxA), an important virulence factor that determines successful pathophysiology. In this study, we investigated the involvement of RtxA from V. Vulnificus in Th17 cell induction through the activation and maturation of DCs. The increased expression of the DC surface marker CD40 caused by V. Vulnificus wild-type infection was reduced by rtxA gene mutation in V. Vulnificus. The mRNA and protein levels of Th17 polarization-related cytokines also decreased in V. Vulnificus rtxA mutant-infected DCs. In addition, the co-culture of Th cells and DCs infected with rtxA mutant V. Vulnificus resulted in reduction in DC-mediated Th17 responses. Th17 cell responses in the small intestinal lamina propria decreased in mice inoculated with V. Vulnificus rtxA 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 rtxA mutation were restored following infection with the rtxA revertant strain. Furthermore, the mutation in the hlyU gene encoding the activator of rtxA1 gene reproduced the results observed with rtxA mutation. Taken together, V. Vulnificus, by means of RtxA, induces inflammatory Th17 responses, which may be associated with adaptive responses of the host against V. Vulnificus infection.
Bibliographical noteFunding Information:
This study was supported by the National Research Foundation of Korea (grant no. NRF-2017R1A2B2009442) and the Creative Materials Discovery Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science ICT and Future Planning (grant no. 2016M3D1A1021387), and also by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry(IPET) through Agriculture, Food and Rural Affairs Research Center Support Program, funded by Ministry of Agriculture, Food and Rural Affairs(MAFRA) (grant no. 710012-03-1-SB110).
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- Dendritic cells
- RTX toxin
- V. Vulnificus
ASJC Scopus subject areas
- Immunology and Allergy