Bile Acid Regulates Mononuclear Phagocytes and T Helper 17 Cells to Control Candida albicans in the Intestine

Abstract

Invasive Candida albicans (CA) infections often arise from the intestine and cause life-threatening infections in immunocompromised individuals. The role of gut commensal microbiota, metabolites, and host factors in the regulation of CA colonization in the intestine is poorly understood. Previous findings from our lab indicate that taurocholic acid (TCA), a major bile acid present in the intestine, promotes CA colonization and dissemination. Here, we report that oral administration of TCA to CA-infected mice significantly decreased the number of mononuclear phagocytes and CD4+ IL17A+ T helper 17 cells that play a critical role in controlling CA in the intestine. Collectively, our results indicate that TCA modulates mucosal innate and adaptive immune responses to promote CA colonization in the intestine.

Keywords: bile acids; fungal colonization; innate and adaptive immunity.

Figure 1

TCA significantly decreased the mononuclear phagocytes in the intestine. Groups of mice infected with ~1 × 10⁷ CFU of CA SC5314 via oral gavage. Control group received sterile drinking water and TCA group received drinking water containing 1% TCA. Eight days post-infection and treatment, mice were euthanized to isolated mononuclear cells from small and large intestine. Cells were labeled with indicated markers to determine macrophages and neutrophils population in the intestine. (A) Representative images; (B) percentage and (C) absolute number of CD11b+ CX3CR1+ phagocytes from small intestine (SI) and large intestine (LI) of untreated and TCA-treated mice were shown. (D) Representative images; (E) percentage and (F) absolute number of CD11b+ F4/80+ macrophages from SI and LI of untreated and TCA-treated mice were shown. (G) Representative images; (H) percentage and (I) absolute number of CD11b+ Ly6G+ neutrophils from SI and LI of untreated and TCA-treated mice were shown. Data shown are combined from 2 independent experiments for a total of 7 to 10 mice per group. Data represent mean ± SEM. The statistical significance of differences between groups was determined by the Mann-Whitney U test with * p ≤ 0.05, ** p ≤ 0.01, and *** p ≤ 0.001.

Figure 2

TCA significantly decreased Th2 and Th17 cells in the intestine. Groups of mice infected with ~1 × 10⁷ CFU CA SC5314 via oral gavage. Control group received sterile drinking water and TCA group received drinking water containing 1% TCA. Eight days post-infection and treatment, mice were euthanized to isolated mononuclear cells from small and large intestine. Cells were labeled with indicated markers to determine Th1, Th2 and Th17 population in the intestine of CA-infected mice. (A) Representative images; (B) percentage and (C) absolute number of CD4+ IFNγ+ T helper 1 cells from small intestine (SI) and large intestine (LI) of untreated and TCA-treated mice were shown. (D) Representative images; (E) percentage and (F) absolute number of CD4+ IL5+ T helper 2 cells from SI and LI of untreated and TCA-treated mice were shown. (G) Representative images; (H) percentage and (I) absolute number of CD4+ IL17A+ T helper 17 cells from SI and LI of untreated and TCA-treated mice were shown. Data shown are combined from 2 independent experiments for a total of 7 to 10 mice per group. Data represent mean ± SEM. The statistical signficance of differences between groups was determined by the Mann-Whitney U test with * p ≤ 0.05, and *** p ≤ 0.001.