Single-cell RNA sequencing reveals how myeloid cell reprogramming by commensal Prevotella enhances defense against Streptococcus pneumoniae lung infection

However, immune interactions with other bacteria influence this dynamic. Depletion of respiratory tract anaerobes including Prevotella is associated with increased mortality from pneumonia, an effect that can be replicated by pre-exposure to Prevotella melaninogenica in mice.

Here, we demonstrate using single-cell RNA sequencing that P. melaninogenica shifts myeloid cell transcriptional profiles during pneumococcal infection from interferon-dominant to pro-phagocytic, correlating with increased S. pneumoniae phagocytosis and clearance from the lung. In neutrophils, improved antibacterial defense was dependent on TNF signaling through TNFR2. Prevotella-enhanced defense also required the recruitment of monocyte-derived macrophages, with selective enrichment of a Cxcl3+ population which differed from the C1qa+ population dominant during S. pneumoniae infection in unprimed mice.