Abstract
INTRODUCTION: Talaromyces marneffei (T. marneffei) is an emerging pathogenic fungus. Macrophage-1 antigen (Mac-1, CR3, CD11b/CD18) is an important receptor on innate immune cells and can recognize pathogens. However, the importance of CR3 in phagocytosis of T. marneffei by macrophages and their responses to T. marneffei have not been clarified. METHODS: We show that interaction of mouse peritoneal macrophages (pMacs) or RAW264.7 macrophages with T. marneffei of its conidia spores and yeast cells enhances CR3 expression on macrophages. The phagocytosis rate was determined using flow cytometry, RT-PCR and Western blotting were used to detect CD11b expression, and the levels of IFN-γ, TNF-α, IL-2, IL-4, IL-6 and IL-10 in the co-culture supernatants were determined by ELISA. RESULTS: Incubation of mouse macrophages with T. marneffei promoted phagocytosis of T. marneffei, which was dramatically mitigated by pretreatment with anti-CD11b antibody or knockdown of CR3 expression on macrophages. Then, interferon γ, tumor necrosis factor α, IL-4, IL-10 and IL-12 production in macrophages incubation with heat-killed T. marneffei was detected. CD11b expression on mouse macrophages was upregulated by T. marneffei. Incubation of T. marneffei promoted phagocytosis of T. marneffei by macrophages and high levels of pro-inflammatory and anti-inflammatory cytokine production by macrophages, which were mitigated and abrogated by pre-treatment with anti-CD11b or knockdown of CD11b expression. CONCLUSION: These data indicated that murine macrophage requires CD11b to recognize Talaromyces marneffei and their cytokine responses to heat-killed T. marneffei in vitro.