Airway bacteria prime innate immune protection against Streptococcus pneumoniae

Abstract

Abstract Commensal (non-pathogenic) bacteria play an important role in protecting against disease. In both humans and animal models, the depletion of commensal bacteria by antibiotics increases susceptibility to pathogen infection of the lung. However, the specific commensal bacteria which contribute to this protective effect remain undefined. In the respiratory tract, Prevotella species are frequently associated with health rather than disease, indicating a potentially beneficial role. Specifically, some Prevotella species negatively correlate with infection with the bacterial pathogen Streptococcus pneumoniae, the most common cause of bacterial pneumonia. We recapitulated this relationship in mice, where we find that exposure to an airway commensal Prevotella species improves rapid clearance of S. pneumoniae from the lung. The use of heat-killed Prevotella was sufficient for inducing protection against S. pneumoniae, which was lost in mice depleted of the pro-inflammatory cytokine TNF-α. These results suggest that Prevotella exposure primes an immune response that increases protection against S. pneumoniae infection in the lung. We further find that mouse neutrophils both secrete TNF-α and are improved in their ability to kill S. pneumoniae following Prevotella exposure. Together, these findings indicate that airway Prevotella species can enhance protection against S. pneumoniae lung infection by activating an innate immune response that increases bacterial clearance.