Interleukin-23 (IL-23) deficiency disrupts Th17 and Th1-related defenses against Streptococcus pneumoniae infection

- Acute response to Streptococcus pneumoniae infection require IL-23 expression.
- Altered pulmonary clearance and susceptibility to dissemination ensues in the absence of IL-23.
- IL-23 deficiency corresponds with a depression in IL-12p70 production.
- In addition to IL-23-mediated abrogation of IL-17 cytokine responsiveness, IFN-γ is affected.
- IL-23 deficiency disrupts the mobilization of neutrophils resulting in pooling of neutrophils in blood.

Resolution of acute of infection caused by capsular Streptococcus pneumoniae infection in the absence of effective antibiotic therapy requires tight regulation of immune and inflammatory responses. To provide new mechanistic insight of the requirements needed for innate host defenses against acute S. pneumoniae infection, we examined how IL-23 deficiency mediated acute pulmonary resistance. We found that IL-23 deficient mice were more susceptible to bacterial colonization in the lungs corresponding with greater bacterial dissemination. The lack of IL-23 was found to decrease IL-6 and IL-12p70 cytokine levels in bronchiolar lavage within the initial day after infection. Pulmonary leukocytes isolated from infected IL-23 deficient mice demonstrated a dramatic decrease in IL-17A and IFN-γ in response to heat-killed organisms. These findings corresponded with significant abrogation of neutrophilic infiltrate in the lungs compared to IL-23 competent mice. Whereas previous studies have shown opposing influences of IL-12/IL-23 regulation, our findings suggest a concordant dependency of IL-23 expression on Th1 and Th17-related responses.