Insights into the role of the respiratory tract microbiome in defense against bacterial pneumonia.

The respiratory tract microbiome (RTM) is a microbial ecosystem inhabiting different niches throughout the airway. A critical role for the RTM in dictating lung infection outcomes is underlined by recent efforts to identify community members benefiting respiratory tract health. Obligate anaerobes common in the oropharynx and lung such as Prevotella and Veillonella are associated with improved pneumonia outcomes and activate several immune defense pathways in the lower airway. Colonizers of the nasal cavity, including Corynebacterium and Dolosigranulum, directly impact the growth and virulence of lung pathogens, aligning with robust clinical correlations between their upper airway abundance and reduced respiratory tract infection risk. Here, we highlight recent work identifying respiratory tract bacteria that promote airway health and resilience against disease, with a focus on lung infections and the underlying mechanisms driving RTM-protective benefits.

Airway Prevotella promote TLR2-dependent neutrophil activation and rapid clearance of Streptococcus pneumoniae from the lung.

This study investigates how specific members of the lung microbiome influence the early immune response to infection. Prevotella species are a major component of the endogenous airway microbiota. Increased abundance of Prevotella melaninogenica correlates with reduced infection with the bacterial pathogen Streptococcus pneumoniae, indicating a potentially beneficial role. Here, we show that P. melaninogenica enhances protection against S. pneumoniae, resulting in rapid pathogen clearance from the lung and improved survival in a mouse lung co-infection model. This response requires recognition of P. melaninogenica lipoproteins by toll-like receptor (TLR)2, the induction of TNFα, and neutrophils, as the loss of any of these factors abrogates Prevotella-induced protection. Improved clearance of S. pneumoniae is associated with increased serine protease-mediated killing by lung neutrophils and restraint of P. melaninogenica-induced inflammation by IL-10 in co-infected mice. Together, these findings highlight innate immune priming by airway Prevotella as an important protective feature in the respiratory tract.