RESUMO
IL-22 plays a critical role in defending against mucosal infections, but how IL-22 production is regulated is incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to Streptococcus pneumoniae lung infection than wild-type animals and that single-nucleotide polymorphisms in IL33 and IL1RL1 were associated with pneumococcal pneumonia in humans. The effect of IL-33 on S. pneumoniae infection was mediated by negative regulation of IL-22 production in innate lymphoid cells (ILCs) but independent of ILC2s as well as IL-4 and IL-13 signaling. Moreover, IL-33's influence on IL-22-dependent antibacterial defense was dependent on housing conditions of the mice and mediated by IL-33's modulatory effect on the gut microbiota. Collectively, we provide insight into the bidirectional crosstalk between the innate immune system and the microbiota. We conclude that both genetic and environmental factors influence the gut microbiota, thereby impacting the efficacy of antibacterial immune defense and susceptibility to pneumonia.
Assuntos
Imunidade Inata , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina 22 , Interleucina-33 , Interleucinas , Streptococcus pneumoniae , Animais , Interleucina-33/imunologia , Interleucina-33/genética , Interleucina-33/metabolismo , Interleucinas/metabolismo , Interleucinas/imunologia , Interleucinas/genética , Camundongos , Streptococcus pneumoniae/imunologia , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/imunologia , Humanos , Camundongos Knockout , Microbiota/imunologia , Camundongos Endogâmicos C57BL , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/microbiologia , Microbioma Gastrointestinal/imunologia , Linfócitos/imunologia , Linfócitos/metabolismo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Several body sites, including the intestinal and respiratory tracts, are colonized with a myriad of bacteria, archaea, fungi, and viruses, which are collectively referred to as the "microbiota." The bacterial component of the microbiota in particular has been recognized to influence a multitude of physiological functions, including innate and adaptive immune responses. Germ-free and microbiota-depleted animals display an impaired antimicrobial defense and are therefore highly susceptible to various infections, including those affecting the lung. In this review, we summarize current understanding of how the microbiota affects antimicrobial immunity and disease tolerance during viral and bacterial pulmonary infections. A better understanding of these mechanisms could help to refine clinical approaches to preserve or rescue the microbiota-immune system interplay and protect patients against lung infections.