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

Kadi J. Horn, Melissa A. Schopper, Zoe G. Drigot and Sarah E. Clark ()
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Kadi J. Horn: University of Colorado School of Medicine, Department of Otolaryngology
Melissa A. Schopper: University of Colorado School of Medicine, Department of Otolaryngology
Zoe G. Drigot: University of Colorado School of Medicine, Department of Otolaryngology
Sarah E. Clark: University of Colorado School of Medicine, Department of Otolaryngology

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-31074-0

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