IL-34 SuppressesCandida albicansInduced TNFαProduction in M1 Macrophages by Downregulating Expression of Dectin-1 and TLR2
Candida albicansis a fungus that is an opportunistic pathogen of humans. Normally,C. albicansexists 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 toC. albicans. IL-34 is a recently discovered cytokine, constitutively 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 M1 macrophages for immunity or anti-inflammatory M2 macrophages for tissue repair. M1 macrophages produce higher levels of inflammatory cytokines such as TNFαin response toC. albicansstimulation. In this study, it was demonstrated that IL-34 attenuated TNFαproduction by M1 macrophages challenged with heat killed Candida (HKC). The molecular mechanism of IL-34 mediated suppression of HKC induced TNFαproduction by M1 macrophages was by the inhibition of M1 macrophage expression of keyC. albicanspattern 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 toC. albicanscolonisation by maintaining low levels TLR2 and Dectin-1 expression by macrophages.