title: Interleukin-23 (IL-23) deficiency disrupts Th17 and Th1-related defenses against Streptococcus pneumoniae infection.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA; Department of Cell Biology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Byung-Jin
authors.initials: BJ
authors.lastname: Kim
authors.forename: Suheung
authors.initials: S
authors.lastname: Lee
authors.forename: Rance E
authors.initials: RE
authors.lastname: Berg
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Simecka
authors.forename: Harlan P
authors.initials: HP
authors.lastname: Jones
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053760:Interleukin-23 Subunit p19 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D015850:Interleukin-6; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: Interleukin-17; Interlukin-23; Neutrophils; Streptococcus pneumoniae