Host cytokine responses distinguish invasive from airway isolates of the Streptococcusmilleri/anginosis group

BACKGROUND The Streptococcus Milleri/Anginosus Group (SMG) colonize mucosal surfaces, especially the airways, and are considered to be normal mucosal microbiota; however, they are a major cause of abscesses, pneumonia and pleural empyema. The production of exoenzymes and virulence factors do not correlate with SMG pathogenicity. Since SMG infections are associated with robust inflammatory responses, we hypothesized that host immune responses might distinguish strains associated with asymptomatic carriage and those associated with fulminant disease. METHODS We measured IL1β, TNF, IL10, IL12, IL23, IL17, and IL4 production from human peripheral blood mononuclear cells (PBMCs) stimulated with a panel of clinical isolates from the airways and infections and measured the ability of these isolates to stimulate TLR2. RESULTS Isolates were categorized based on the levels of cytokines they induced from PBMCs (high, intermediate, low). Airway isolates predominantly induced low levels of cytokines and isolates from invasive disease induced higher levels, although about 10% of the strains produced divergent cytokine responses between donors. Interestingly, the donors were most divergent in their production of IL17, IL12 and IL23. CONCLUSIONS We propose that the ability to inhibit or avoid an inflammatory response is associated with carriage in the airways and variability in responses between isolates and donors might contribute to susceptibility to disease.