Environmental bioaerosol antigen Methanosphaera stadtmanae induces a TH17 inflammatory lung response via TLR4 signaling

Bioaerosolsin occupational environments are highly associated with the development of inflammatory lung diseases. The archaeaspecie Methanosphaera stadtmanae(MSS) is found in high concentrations in poultries, dairy farms and swine confinement buildings bioaerosols(up to 10 8 archaea/m 3 ). MSS induces a strong specie-dependent inflammatory lung response in mice, characterized by T cells, eosinophils, neutrophils, and IgG production. However, the polarity of lung response induced by MSS and the mechanisms underlying this inflammatory response remain unknown. Using a mouse model, we show that MSS induced a weak T H 2 (CD4 + /IL-13 + T cells) strong T H 17 (CD4 + /IL-17A + T cells) lung response, characterized by IgG 1 (but not IgG 2a and IgE) production. Moreover, mice did not develop airway hyperresponsiveness following MSS exposure. Interestingly, increasing MSS quantity led to a lower eosinophil count associated with a decreased T H 2 response. Using transgenic mice, we found that eosinophils, mast cells and ILC2 cells are not required for the T H 2 and T H 17 inflammatory response to MSS. However, Tlr4−/− mice (but not Tlr2−/− ) had reduced airway inflammation compared to WT mice after exposure to MSS, indicating a crucial role for TLR4activation in this specific response. Finally, heat denaturation and zymographystudies suggested TLR4activation likely occurs through MSS protein antigen recognitionrather than by enzymatic activity and cell damage. We conclude that MSS induces a T H 17 inflammatory lung response via TLR4signaling.