Background Talaromyces marneffei ( T. marneffei ) is a destructive opportunistic dimorphic fungal which can cause lethiferous Talaromycosis, but the clearance of T. marneffei mainly depends on the innate immune response. Objective To investigate whether T. marneffei can inhibit the expression of CD86 in THP-1 cells after infection and discuss the potential mechanisms. Methods Western blot and immunoelectron microscopy were used to detect the CD86 expression on T. marneffei cultured on BHI medium at 37°C. Western blot, enzyme-linked immunoassay and immunofluorescence were used to detect the change of CD86 expression on macrophages incubating with T. marneffei . Enzyme-linked immunoassay was used to detect the content of CD86 in supernatant in the co-culture system. Immunohistochemistry and immunoelectron microscopy were used to detect the expression of CD86 on T. marneffei incubating with macrophages. Results T. marneffei did not express CD86 when cultured separately at 37°C detected by Western blot and immunoelectron microscopy, but it did express CD86 when incubated with macrophages detected by immunohistochemistry and immunoelectron microscopy. The CD86 expression of macrophages significantly decreased at 72 hours when infected with T. marneffei while the content of CD86 in supernatant significantly increased at 72 hours compared with the control group which were detected by Western blot, enzyme-linked immunoassay and immunofluorescence. Conclusion 1) After T. marneffei infection, CD86 expression on THP-1 decreased, and with the progression of infection, insufficient polarization of M1 macrophages gradually appeared; 2) T. marneffei may adsorb or uptake CD86 in supernatant produced by macrophages during the contact with THP-1 cells, thus leading to the consumption of CD86 in macrophages.

Background: Talaromyces Marneffei (T.marneffei) is an destructive opportunistic dimorphic fungal which can cause lethiferous Talaromycosis, but the clearance of T.marneffei mainly depends on the innate immune response. Objectives: To investigate the effect of T.marneffei on CD86 expression in THP-1 cells after infection and discuss the potential mechanisms. Methods: Western blot and immunoelectron microscopy were used to detect the CD86 expression on T.marneffei cultured on BHI medium at 37℃. Western blot、enzyme-linked immunoassay and immunofluorescence were used to detect the change of CD86 expression on macrophages incubating with T.marneffei. Enzyme-linked immunoassay was used to detect the content of CD86 in supernatant in the co-culture system. Immunohistochemistry and immunoelectron microscopy were used to detect the expression of CD86 on T.marneffei incubating with macrophages. Results: T.marneffei didn’t express CD86 when cultured separately at 37℃ detected by western blot and immunoelectron microscopy, but it did express CD86 when incubated with macrophages detected by immunohistochemistry and immunoelectron microscopy. The CD86 expression of macrophages significantly decreased at 72 hours when infected with T.marneffei while the content of CD86 in supernatant significantly increased at 72 hours compared with the control group which were detected by western blot, enzyme-linked immunoassay and immunofluorescence. Conclusion: 1.After T.marneffei infection，CD86 expression on THP-1 decreased，and with the progression of infection, insufficient polarization of M1 macrophages gradually appeared；2.T.marneffei may adsorb or uptake CD86 in supernatant produced by macrophages during the contact with THP-1 cells, thus leading to the consumption of CD86 in macrophages.

The opportunistic fungal pathogen Talaromyces marneffei, which is endemic across a narrow band of tropical Southeast Asia and southern China, is an intracellular pathogen that causes systemic and lethal infection through the mononuclear phagocyte system. The mechanisms by which T. marneffei successfully replicates and escapes the immune system remain unclear. To investigate the role of arginine metabolism in the escape of T. marneffei from killer macrophages, we assessed inducible nitric oxide synthase (iNOS) and arginase expression, nitric oxide (NO) production, arginase and phagocytic activity, and the killing of T. marneffei in a coculture system. Our results indicate that T. marneffei induced macrophage polarization toward the M2 phenotype and regulated the arginine metabolism pathway by prolonging infection, thereby reducing antimicrobial activity and promoting fungal survival. Moreover, inhibiting T. marneffei–induced macrophage arginase activity with Nω-hydroxy-nor-arginine restored NO synthesis and strengthened fungal killing. These findings indicate that T. marneffei affects macrophage polarization and inhibits macrophage antimicrobial function via the arginine metabolism pathway.

Background Macrophages are the first line of defense against Talaromyces marneffei . CD86 is a surface molecule expressed on antigen‐presenting cells, such as macrophages, that provide costimulatory signals necessary for T cell activation and survival. In a prior study, it was shown that as infection progressed, CD86 expression levels in macrophages considerably declined while CD86 concentrations in the supernatant significantly increased. Additionally, M1 macrophage polarization was insufficient and switched to M2 macrophage polarization. Besides costimulation, however, additional roles of CD86 are not known or well‐studies. Therefore, we hypothesized that upregulating CD86 on macrophages might promote T. marneffei defense. Methods A lentivirus vector, called Lenti‐CD86, was used to infect THP‐1 cells to overexpress secretory CD86. Through killing assay, nitric oxide detection, and cytokine detection, the capacity of THP‐1 macrophages to phagocytose and kill T. marneffei was examined. Results In the current study, Lenti‐CD86 transfection of THP‐1 cells resulted in a signifant expression of CD86. Additionally, the THP‐1 macrophages stably transfected with Lenti‐CD86 showed higher nitric oxide and IL‐1β production, faster polarization, and stronger phagocytosis and killing capabilities than the non‐transfected or control virus transfected cells. Conclusion Our study shows that lentivirus‐mediated CD86 overexpression improves THP‐1 macrophages' capacity to phagocytose and eliminate T. marneffei .