title: IL-12 administered during Chlamydia psittaci lung infection in mice confers immediate and long-term protection and reduces macrophage inflammatory protein-2 level and neutrophil infiltration in lung tissue.
abstract: Protection against infections with the intracellular bacterium Chlamydia spp. requires Th1-polarized CD4+ T cell immunity. In BALB/c mouse lung infections, immediate innate and nascent Chlamydia-specific immune responses following intranasal inoculation of Chlamydia psittaci strain B577 were modulated by 7-day i.p. administration of murine rIL-12, the initiation cytokine for Th1 immunity. Treatment with IL-12 reduced the severity of chlamydial pneumonia, abolished mortality (37.5% in untreated mice), and significantly reduced numbers of chlamydial organisms in lungs. On day 4 after inoculation, the neutrophil:macrophage ratio in bronchointerstitial pneumonias was 1.96 in untreated mice and 0.51 in IL-12-treated mice. This immediate, IL-12-mediated shift in innate inflammatory phenotype was correlated with a significant reduction of lung concentrations of the neutrophil chemoattractant macrophage inflammatory protein (MIP)-2 (putative murine homologue of human IL-8), monocyte chemotactic protein-1, and TNF-alpha; and a reduction in MIP-1alpha and IFN-gamma, at high-dose infection only, and IL-12-independent IL-10 levels. Chlamydia-specific Ab titers and Ig isotype ratios indicated an IL-12-dependent Th1 shift. Recall responses of IL-12-primed mice to secondary chlamydial lung infection eliminated chlamydiae more effectively and generated a lung cytokine profile conducive to perpetuation of the Th1 memory population. These data support the hypothesis that genetic differences in endogenous IL-12 production and response pathways could determine disease outcomes characterized by poor chlamydial clearance and a purulent inflammatory infiltrate vs effective elimination of chlamydiae in a macrophage-dominated response.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Auburn University, AL 36849, USA.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: M D
authors.initials: MD
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Lenz
authors.forename: D
authors.initials: D
authors.lastname: Gao
authors.forename: B
authors.initials: B
authors.lastname: Kaltenboeck
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D054426:Chemokine CXCL2; D002690:Chlamydia Infections / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D002691:Chlamydophila psittaci / Q000276:immunology; D005260:Female; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000627:therapeutic use; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D015846:Monokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D016019:Survival Analysis; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism