NLRP3 inflammasome activation contributes to fungal clearance and lung injury during Talaromyces marneffei infection

The increased levels of IL-1 & beta; and IL-18 cytokines have been associated with the severity of sepsis and outcomes of patients infected with Talaromyces marneffei. Previous studies have suggested that NLRP3 plays an important role in caspase-1 activated secretion of IL-1 & beta; and IL-18 in fungal-infected macrophages. In the present study, the role of the NLRP3 inflammasome in talaromycosis is investigated in an in vitro assay and in vivo with a mice systemic infection model. We found that the NLRP3 inflammasome pathway in infected mice is activated along with increased production of IL-1 & beta;. Such an activation of the NLRP3 inflammasome is also observed in either mice or human macrophages challenged with T. marneffei conidia. Our results indicate that IL-1 & beta; release by infected macrophages is NLRP3 inflammasome-dependent and NLRP3 contributes to death of mice at the early stage of pulmonary infection. Moreover, a greater number of MPO-positive cells are found in the lungs of infected Nlrp3-/  mice and WT mice with reduced LDH levels, especially at the last stage of infection. Therefore, we conclude that the NLRP3 Inflammasome activation is important for fungal clearance, neutrophil recruitment and lung injury during T. marneffei Infection.

Automated summary

This study investigates the role of the NLRP3 inflammasome in Talaromyces marneffei infection. The results show that this pathway is activated in infected mice and macrophages, leading to the release of IL-1β and contributing to early-stage mortality in pulmonary infection.