Early life exposure to Streptococcus pneumonia has sex-specific long-term impact on inflammatory responses

Abstract INTRODUCTION Lung microbiota plays a central role in health and disease development. Recently, recurrent viral infections in preschool age children were associated with lung microbiota carriage of Streptococcus pneumonia (SP). In addition, immune development and inflammatory responses have sexual dimorphism, but it is still controversial whether there is sex-specific microbiota composition. OBJECTVE Given that immune development occurs early in life, the objective of this project is to evaluate the consequences of early life lung microbiota alteration by SP exposure on inflammatory response later in life. METHODS Neonatal Brown Norway rats were exposed to SP via intranasal administration (sub inflammatory dose). Lung microbiota was assessed until weaning age (21 days old), using v3–v4 16S rRNA sequencing. At 8 weeks old (post-puberty), rats were infected with LPS and their inflammatory responses were assessed 24h post using bronchoalveolar lavage (BAL). RESULTS Early life exposure to SP reduced lung microbiota diversity and impacted its constitution until weaning age. Although control females exposed to LPS had higher inflammatory response than control males, early life exposure to SP significantly reduced BAL inflammatory cell recruitment in females but not in SP-males. Opposingly, in SP-males, the inflammatory response shifted from a neutrophilic response to a more eosinophilic inflammation. CONCLUSION Early life exposure to SP modulated both lung microbiota and immune responses later in life. The sex-specific immune modulation by lung microbiota composition in early life could have large implication for many inflammatory diseases presenting sexual bias. Supported by grants from Quebec Health Research Network and Fondation IUCPQ (Quebec, Canada).