Gut colonization byCandida albicansaggravates inflammation in the gut and extra-gut tissues in mice

Abstract

We examined whether Candida albicans gut colonization aggravates immune diseases in mice. Chronic and latent C. albicans gut colonization was established by the intragastric inoculation of C. albicans in mice fed as part of a purified diet. Allergic diarrhea was induced by repetitive intragastric administration of ovalbumin in sensitized BALB/c mice. Contact hypersensitivity was evaluated by measuring ear swelling after topical application of 2, 4-dinitrofluorobenzene in NC/Nga mice. Arthritis was induced by intradermal injection of bovine type-II collagen emulsified with complete Freund's adjuvant in DBA/1J mice. C. albicans gut colonization increased the incidence of allergic diarrhea, which was accompanied by gut hyperpermeability, as well as increased infiltration of inflammatory cells in the colon. Contact hypersensitivity was also exacerbated by C. albicans gut colonization, as demonstrated by increased swelling, myeloperoxidase activity, and proinflammatory cytokines in ear auricles. Furthermore, C. albicans gut colonization promoted limb joint inflammation in collagen-induced arthritis, in an animal model of rheumatoid arthritis. These findings suggest that C. albicans gut colonization in mice aggravates inflammation in allergic and autoimmune diseases, not only in the gut but also in the extra-gut tissues and underscores the necessity of investigating the pathogenic role of C. albicans gut colonization in immune diseases in humans.

Cell Wall Polysaccharides of <i>Candida albicans</i> Induce Mast Cell Degranulation in the Gut

“…We previously observed that C. albicans gut colonization promoted the infiltration and degranulation of mast cells in the mouse stomach and colon [3, 4]. In the present study, the histochemical examination of gastric mucosa showed infiltration of a number of mast cells in C. albicans -colonized mice and that degranulation was evident in the majority of cells (Fig.…”

“…We previously observed that serum antibody responses to repeated oral administration of ovalbumin (OVA) and gastrointestinal uptake of orally administered OVA were enhanced by C. albicans gut colonization in mice [3]. In addition, C. albicans gut colonization aggravated OVA-induced allergic diarrhea, 2,4-dinitrofluorobenzene-induced contact skin hypersensitivity, and type-II collagen-induced arthritis in mice [4]. These findings suggest that C. albicans gut colonization is not only a risk factor for food allergy but also an aggravating factor for inflammation in allergic and autoimmune diseases.…”

“…These findings suggest that C. albicans gut colonization is not only a risk factor for food allergy but also an aggravating factor for inflammation in allergic and autoimmune diseases. Mechanistically, mast cell-mediated hyperpermeability of the gut mucosal epithelium is likely to be responsible for the enhanced uptake of orally administered OVA and OVA-induced allergic diarrhea in C. albicans -colonized mice [3, 4]. However, the mechanism by which C. albicans colonization influences mast cell function in the gut mucosa is unclear.…”

Exposure to Candida albicans Polarizes a T-Cell Driven Arthritis Model towards Th17 Responses, Resulting in a More Destructive Arthritis

“…In the arthritic joint, direct or indirect effects of IL-17/Th17 result in increased inflammation, angiogenesis, and osteoclastogenesis, resulting in enhanced breakdown of cartilage and bone [11]–[14]. Although C. albicans or Candida -derived β-glucan have been shown to induce and aggravate various models of arthritis [15], [16], these observations have not yet been linked to modulation of the IL-17/Th17 pathway and increased structural damage.…”

Gut Colonization by <i>Candida albicans</i> Inhibits the Induction of Humoral Immune Tolerance to Dietary Antigen in BALB/c Mice

“…Based on the above, it is unlikely that the cell constituents of C. albicans directly promote antibody production in splenocytes restimulated by an antigen and abrogate already established oral tolerance in splenocytes. Although Tokunaka et al reported that intraperitoneal administration of β-D-glucan, a cell-wall constituent of C. albicans , along with bovine serum albumin (BSA) promoted an increase in serum anti-BSA IgG in mice [22], our previous study showed that the serum concentrations of β-D-glucan in C. albicans -colonized mice did not differ from those of the control mice [23]. In our model of C. albicans -colonized mice, therefore, it is unlikely that β-D-glucan released from C. albicans is absorbed in the gut and then contributes to the inhibition of antigen feeding-induced suppression of serum antibodies.…”