Th17 cells differentiated with mycelial membranes of Candida albicans prevent oral candidiasis

Abstract

Candida albicans is a human commensal that causes opportunistic infections. Th17 cells provide resistance against mucosal infection with C. albicans; however, the T cell antigens remain little known. Our final goal is to find effective T cell antigens of C. albicans that are responsible for immunotherapy against candidiasis. Here, we prepared fractions including cytosol, membrane and cell wall from yeast and mycelial cells. Proteins derived from a membrane fraction of mycelial cells effectively induced differentiation of CD4+ T cells into IL-17A-producing Th17 cells. To confirm the immunological response in vivo of proteins from mycelial membrane, we performed adoptive transfer experiments using ex vivo stimulated CD4+ T cells from IL-17A-GFP reporter mice. Mycelial membrane-differentiated CD4+ Th17 cells adoptively transferred intravenously prevented oral candidiasis by oral infection of C. albicans, compared with control anti-CD3-stimulated CD4+ T cells. This was confirmed by the clinical score and the number of neutrophils on the infected tissues. These data suggest that effective T cell antigens against candidiasis could be present in the membrane protein fraction of mycelial cells. The design of novel vaccination strategies against candidiasis will be our next step.

Dispensable Role of Aire in CD11c+ Conventional Dendritic Cells for Antigen Presentation and Shaping the Transcriptome

“…A 100 μg/ml C. albicans mycelial membrane protein (MP) fraction from C. albicans SC5314 ( 25 ) was prepared as previously described ( 26 ). Then, 200 μl of a 1:1 emulsion of C. albicans mycelial MP fraction and CFA ( Candida /CFA) was injected into mice (s.c.).…”

Pathobiont-responsive Th17 cells in gut-mouth axis provoke inflammatory oral disease and are modulated by intestinal microbiome

“…In vitro stimulation of CD4 + T cells was performed as descried in previous reports (Hashimoto et al, 2017;Tasaki al., 2018). Briefly, bone marrow (BM) cells were harvested from femurs and tibias of B6 mice.…”

Candida-Associated Denture Stomatitis and Murine Models: What Is the Importance and Scientific Evidence?

“…Moreover, the clinical and histologic findings in the rats' palatal tissues of experimental CADS are similar to those of humans [39]. Despite these advantages, a literature search on induction of this lesion in rat models revealed only a few related studies [28][29][30][31][32][33][34] since most previous investigations on murine oral candidosis used mice as experimental animals with lesions induced on the dorsum of the animal's tongue [28][29][30][31][32][33][34][35][36][37][38]. Therefore, these latter studies can be considered only indirectly since mice have a small oral cavity for the use of palatal denture-like appliances, which are essential for CADS induction [28][29][30][31][32][33][34][35][36][37][38].…”

“…Investigation of oral candidosis using animals has often been carried out in murine models, which are developed in small rodent animals like mice, rats and hamsters [28][29][30][31][32][33][34][35][36][37][38]. These animals have demonstrated colonization patterns and lesions of oral candidosis similar to those observed in humans both microscopically and histologically [39,40].…”