Candida albicans cell wall mannoprotein synergizes with lipopolysaccharide to affect RAW264.7 proliferation, phagocytosis and apoptosis

Abstract

With the widespread use of invasive surgery, immunosuppressive therapy and broad-spectrum antibiotics, there has resulted a corresponding increase in severe systemic infections as produced by Candida albicans (C.albicans), as it combines with bacterial infections. Such infections often result in high rates of mortality. In this report, we examined the effects of the C. albicans cell wall mannoprotein (MP) on macrophage immunity. The MTS assay was used to detect cell proliferation activity and neutral red staining to observe cell phagocytosis. The Griess method was used to detect NO secretion in culture supernatants and apoptosis of macrophages were determined with use of FITC-Annexin V and PI staining. mRNA and protein expressions of JAK2, STAT3, IL-1β, IL-6, TNF-α and iNOS in RAW264.7 cells were determined with use of RT-PCR and western blot. MP significantly promoted the proliferation of RAW264.7 cells, inhibited their phagocytic capacity, but exerted no significant effects on apoptosis of macrophages. In addition, MP not only up-regulated the expression of cytokines, but also the expressions of p-stat3 and p-jak2. Interestingly, when MP was combined with lipopolysaccharide (LPS) a markedly accentuated release of inflammatory cytokines was observed. MP promotes macrophage inflammation induced by LPS and participates in the inflammatory response. One of the potential mechanisms of this effect involves MP activation of the JAK2/STAT3 signaling pathway in RAW264.7 cells, which enables macrophages to transform from M0 to M1 and promote the occurrence of inflammation.