IL-34 Suppresses Candida albicans Induced TNFalpha Production in Ml Macrophages by Downregulating Expression of Dectin-1 and TLR2

摘要

Candida albicans is a fungus that is an opportunistic pathogen of humans. Normally, C. albicans exists as a harmless commensal and does not trigger inflammatory responses by resident macrophages in skin mucosa, which may be caused by a tolerance of skin macrophage to C. albicans. IL-34 is a recently discovered cytokine, cpnstitutively expressed by keratinocytes in the skin. IL-34 binds to the receptor of M-CSF, thereby stimulating tissue macrophage maturation and differentiation. Resident macrophages exhibit phenotypic plasticity and may transform into inflammatory Ml macrophages for immunity or anti-inflammatory M2 macrophages for tissue repair. Ml macrophages produce higher levels of inflammatory cytokines such as TNFa in response to C. albicans stimulation. In this study, it was demonstrated that IL-34 attenuated TNFa production by Ml macrophages challenged with heat killed Candida (HKC). The molecular mechanism of IL-34 mediated suppression of HKC induced TNFa production by Ml macrophages was by the inhibition of Ml macrophage expression of key C. albicans pattern recognition receptors (PPRs), namely, Toll-like receptor (TLR) 2 and Dectin-1. The results of this study indicated that constitutive IL-34 expressed by skin keratinocytes might suppress resident macrophage responses to C. albicans colonisation by maintaining low levels TLR2 and Dectin-1 expression by macrophages.