Abstract
BackgroundPenicillium marneffei (P. marneffei) is a thermally dimorphic fungus pathogen that causes fatal infection. Alveolar macrophages are innate immune cells that have critical roles in protection against pulmonary fungal pathogens and the macrophage polarization state has the potential to be a deciding factor in disease progression or resolution. The aim of this study was to investigate mouse alveolar macrophage polarization states during P. marneffei infection.ResultsWe used enzyme-linked immunosorbent (ELISA) assays, quantitative real-time PCR (qRT-PCR), and Griess, arginase activity to evaluate the phenotypic markers of alveolar macrophages from BALB/C mice infected with P. marneffei. We then treated alveolar macrophages from infected mice with P. marneffei cytoplasmic yeast antigen (CYA) and investigated alveolar macrophage phenotypic markers in order to identify macrophage polarization in response to P. marneffei antigens. Our results showed: i) P. marneffei infection significantly enhanced the expression of classically activated macrophage (M1)-phenotypic markers (inducible nitric oxide synthase [iNOS] mRNA, nitric oxide [NO], interleukin-12 [IL-12], tumor necrosis factor-alpha [TNF-α]) and alternatively activated macrophage (M2a)-phenotypic markers (arginase1 [Arg1] mRNA, urea) during the second week post-infection. This significantly decreased during the fourth week post-infection. ii) During P. marneffei infection, CYA stimulation also significantly enhanced the expression of M1 and M2a-phenotypic markers, consistent with the results for P. marneffei infection and CYA stimulation preferentially induced M1 subtype.ConclusionsThe data from the current study demonstrated that alveolar macrophage M1/M2a subtypes were present in host defense against acute P. marneffei infection and that CYA could mimic P. marneffei to induce a host immune response with enhanced M1 subtype. This could be useful for investigating the enhancement of host anti-P. marneffei immune responses and to provide novel ideas for prevention of P. marneffei-infection.
Highlights
Penicillium marneffei (P. marneffei) is a thermally dimorphic fungus pathogen that causes fatal infection
A typical mold was observed as hyaline filamentous forms with branches, sometimes with chains of smooth conidia giving the appearance of a brush compatible with P. marneffei after Lactophenol cotton blue staining (Fig. 1b)
The results suggested that cytoplasmic yeast antigen (CYA) stimulation enhanced Classically activated macrophage (M1) and Alternatively activated macrophage (M2a) macrophage polarization, which was consistent with the results for P. marneffei infection
Summary
Penicillium marneffei (P. marneffei) is a thermally dimorphic fungus pathogen that causes fatal infection. Alveolar macrophages are innate immune cells that have critical roles in protection against pulmonary fungal pathogens and the macrophage polarization state has the potential to be a deciding factor in disease progression or resolution. HIV patients successfully treated for P. marneffei infection should receive long-term maintenance therapy to prevent recurrence [6]. Most opportunistic infections, such as Cryptococcus neoformans, Aspergillus fumigatus, and Pneumocystis, rely more heavily on innate immunity when they are T cell deficient. Macrophages are innate immune cells that have critical roles in protection against pulmonary fungal pathogens, including C. neoformans, A. fumigatus, Pneumocystis and Candida albicans [7,8,9,10]. Macrophage polarization state has the potential to be a deciding factor in disease progression or resolution [11]
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