The microbiota plays a critical role in the reactivity of lung immune components to innate ligands

Abstract

The lung has long been considered a sterile organ devoid of microbiota. The process of colonization of the lung by a microbiota raises the question of its influence on the maturation of the pulmonary epithelial barrier and on the development of immunity. Alterations in the pulmonary microbiota have been reported in patients with respiratory diseases, such as asthma or bronchiolitis mainly caused by respiratory syncytial virus (RSV) in young children. Thus, we examined the extent to which the responsiveness of lung tissue to stimuli to innate immunity receptor agonists, Toll-like Receptors (TLRs), and to RSV, is controlled by the endogenous microbiota.&nbsp;To answer this question, we compared the reactivity of lung explants or alveolar macrophages (AM) of germ-free mice (GF) to specific pathogen-free mice (SPF) to produce cytokines following exposure to various ligands of TLRs or to RSV. Inflammatory markers were measured in the airways at different times after nasal instillation of LPS in GF and SPF mice.&nbsp;<i>Ex vivo</i> stimulation by different ligands of TLRs or RSV infection of lung explants or AM from GF mice lead to faster and stronger cytokine production than those generated from SPF mice. In addition, GF mice instilled with LPS exhibit faster lung tissue inflammatory response and neutrophil recruitment compared to SPF mice.&nbsp;The GFs context, whether <i>ex vivo</i> or <i>in vivo</i>, was always associated with increased reactivity characterized by increased expression of cytokines or type-I interferons pathways. The presence of a microbiota is an element participating in the moderation of the immune response of the pulmonary mucosa and consequently, would affect the sensitivity of the lungs to pathogens.