STAT1 drives M1 macrophage polarization during Aspergillus fumigatus infection.

BACKGROUND

Macrophages exhibit distinct polarization states (M1/M2) in response to inflammatory stimuli. However, the molecular mechanisms regulating macrophage polarization during Aspergillus fumigatus infection remain incompletely understood.

OBJECTIVE

This study aims to investigate the role of signal transducer and activator of transcription 1 (STAT1) in modulating macrophage polarization during A. fumigatus-induced invasive pulmonary aspergillosis (IPA).

METHODS

An IPA mouse model and THP-1-derived macrophages were used to evaluate STAT1 expression and macrophage phenotype. Techniques included immunohistochemistry, immunofluorescence, Western blotting, ELISA, flow cytometry, and RT-qPCR.

RESULTS

In vivo, IPA led to increased infiltration of M1 macrophages and elevated STAT1, P-STAT1, IFN-γ, and iNOS levels in lung tissues, while the expression of M2 markers (Arg1, FIZZ1) remained unaltered. In vitro, exposure to A. fumigatus conidia promoted STAT1 expression and M1 polarization in THP-1 cells, with no significant effect on the M2 marker Arg1. Both pharmacological inhibition of STAT1 with fludarabine and genetic silencing of STAT1 by siRNA significantly attenuated the expression of M1 markers and pro-inflammatory cytokines, while STAT1 overexpression enhanced the expression of M1 markers and pro-inflammatory cytokines.

CONCLUSION

STAT1 is a central regulator of M1 macrophage polarization in response to A. fumigatus infection. Targeting STAT1 may represent a potential therapeutic approach for managing invasive aspergillosis by modulating host immune responses.