Recognition and Blocking of Innate Immunity Cells by Candida albicans Chitin

Abstract

Chitin is a skeletal cell wall polysaccharide of the inner cell wall of fungal pathogens. As yet, little about its role during fungus-host immune cell interactions is known. We show here that ultrapurified chitin from Candida albicans cell walls did not stimulate cytokine production directly but blocked the recognition of C. albicans by human peripheral blood mononuclear cells (PBMCs) and murine macrophages, leading to significant reductions in cytokine production. Chitin did not affect the induction of cytokines stimulated by bacterial cells or lipopolysaccharide (LPS), indicating that blocking was not due to steric masking of specific receptors. Toll-like receptor 2 (TLR2), TLR4, and Mincle (the macrophage-inducible C-type lectin) were not required for interactions with chitin. Dectin-1 was required for immune blocking but did not bind chitin directly. Cytokine stimulation was significantly reduced upon stimulation of PBMCs with heat-killed chitin-deficient C. albicans cells but not with live cells. Therefore, chitin is normally not exposed to cells of the innate immune system but is capable of influencing immune recognition by blocking dectin-1-mediated engagement with fungal cell walls.

Fungal Morphogenesis

“…Therefore, morphological and physiological plasticity allows fungi to rapidly adapt to changing extracellular conditions. Species-specific signaling and morphological features appear to be a direct result of fungal attempts to survive as new microenvironments, and their particular cell stresses, were encountered (Hogan and Klein 1994;Newman et al 1995;Batanghari et al 1998;Sebghati et al 2000;Gow et al 2002;Brandhorst et al 2004;Rappleye et al 2004Rappleye et al , 2007Gantner et al 2005;Nemecek et al 2006;Gauthier and Klein 2008;Nather and Munro 2008;Mora-Montes et al 2011;. The concerted action of morphotype and physiological changes in the context of a particular environment are therefore critical for successful fungal adaptation (Butler et al 2009;O'Connor et al 2010).…”

The role of pattern recognition receptors in the innate recognition ofCandida albicans

“…Glucans are key fungal PAMPs. 18,19,118 A recent study revealed that glucans from C. albicans hyphae are different from those from yeast cells. Hyphal glucan induces robust immune responses in human PBMCs and macrophages via a Dectin-1-dependent mechanism.…”

“…On human peripheral blood mononuclear cells (PBMCs) and murine macrophages, purified chitin from C. albicans could block the recognition of C. albicans yeast cells. 19 A recent study revealed that purified chitin particles derived from C. albicans led to the selective secretion of the anti-inflammatory cytokine IL-10 on murine bone marrow-derived macrophages, 122 and NOD2, TLR9 and MR are essential fungal chitin-recognition receptors for this response. 122 The recognition of C. albicans by PRRs is generally thought to occur at the phagocytic cell surface and this process leads to the phagocytosis of C. albicans and the formation of an intracellular vacuole called phagosome.…”

“…Although the basic components of the cell wall are similar, the precise structure and chemical properties are different in different forms of C. albicans, which may facilitate host immune system to recognize different cell forms. 18,19 Host innate immunity to C. albicans critically requires pattern recognition receptors (PRRs). PRRs is fundamental in discriminating self from non-self via recognizing vital conserved chemical signatures of pathogens, called pathogen-associated molecular patterns (PAMPs).…”

Chitosan but Not Chitin Activates the Inflammasome by a Mechanism Dependent upon Phagocytosis

“…Possible explanations for these disparate findings include different sources (e.g. shrimp, crab, fungal) and manufacturing processes utilized to make the glycans, resulting in variability in the tertiary structure of the polymers and in the degree of contaminants (13,19). Chitin is frequently isolated from crustacean waste products and is naturally associated with protein and minerals that are difficult to remove.…”