Modulation of human monocytes by the pathogenic fungus Candida albicans
As part of the normal flora in the human body C. albicans acts as an opportunistic microbe but can also cause superficial and systemic infections. As a part of cellular immune defense mechanisms, monocytes directly phagocytose, release extracellular DNA traps (MoETs), and secrete cytokines in response to C. albicans. The cytokine secretion by monocytes is enhanced by complement activation in the human serum. However, Candida albicans has the ability to bind human complement regulators onto its surface to evade complement attack. One of these regulators is complement factor H which inhibits further complement activation, limiting recognition and contact with immune cells and enhancing the survival of the pathogenic fungus. The bound factor H modulates cytokine secretion of monocytes in similar pattern when bound onto apoptotic HUVEC cells, which is known to be immunologically silent. This modulation of cytokine secretion creates a favorable condition for the pathogen to survive. Moreover, the secreted cytokines by factor H-modulated monocytes also strong enough to induce differentiation of naive T cells into induced regulatory T cells which dampens further immune reaction. Taken together, this study shows a new immune evasion mechanism by C. albicans by modulating human monocytes response by utilizing human complement regulator. ...