Investigating asthma-associated respiratory tract Firmicutes species in the regulation of Type-2 immunity

Increased burden in the lower airways of certain members of the phyla Firmicutes, including Staphylococcus and Streptococcus species, and a reduction in Veillonella, have been associated with the pathogenesis of allergic asthma. It is unclear whether these associations contribute to disease pathogenesis or engender a suppressive environment that attenuates pathology. We hypothesise that respiratory tract Firmicutes stimulate regulatory immune responses in the airways that can ameliorate immunopathology in allergic asthma. In vitro, we found that Staphylococcus aureus, Streptococcus pneumoniae and Veillonella parvula all stimulated strong IL-10 production, particularly in primary murine macrophages, which had the capacity to suppress cytokine secretion by Th2-polarised splenocytes. Moreover, monocolonisation of germ-free mice with S.aureus stimulated a strong IL-10 response in the lungs that was largely contained in the innate immune compartment. Using a murine model of allergic airway inflammation, we demonstrate that intranasal exposure of mice to Staphylococcus aureus or Veillonella parvula promotes significantly elevated IL-10 production by monocyte-derived macrophages and CD4 T cells in the airways and lung tissue of mice following allergen challenge. We also found significantly reduced expression of the Th2 cell chemoattractant CCL17 in the lungs of S. aureus-colonised mice. Concurrent with these protective responses, we saw attenuated inflammatory features in the airways, including decreased Th2 cytokine responses and reduced eosinophil accumulation in the bronchoalveolar space, compared to PBS-administered controls. Our data supports the hypothesis that exposure of lung macrophages to respiratory tract Firmicutes bacteria, including S.aureus, S.pneumoniae and V.parvula, can engender an immunosuppressive environment that regulates Th2 cell effector function and dampens allergic airway inflammation.