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Infect. Immun. doi:10.1128/IAI.01329-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The IL-23/IL-17 Cytokine Axis in Murine Pneumocystis Infection

Section of Pulmonary/Critical Care Medicine, LSU Health Sciences Center, New Orleans, LA

	Abstract

Host defense mechanisms against P. carinii are not fully understood. Previous work in the murine model has shown that host defense against infection is critically dependent upon host CD4⁺ T cells. The recently described Th17 immune response is predominantly a function of effector CD4+ T cells stimulated by IL-23, but whether these cells are required for defense against P. carinii infection is unknown. We tested the hypothesis that P. carinii stimulates the early release of IL-23, leading to an increased IL-17 production and lung effector CD4⁺ T cell population, mediating clearance of infection. In vitro, stimulation of alveolar macrophages with P. carinii induced IL-23, and IL-23p19 mRNA was expressed in lungs of mice infected with this pathogen. To address the role of IL-23 in resistance to P. carinii, IL-23p19-/- and wild type control C57BL/6 mice were infected and their fungal burden and cytokine/chemokine responses were compared. IL-23p19-/- mice displayed transient but impaired clearance of infection which was most apparent two weeks after inoculation. In confirmatory studies, administration of either anti IL-23p19 or anti IL-17 neutralizing antibody to WT mice infected with P. carinii also caused increases in fungal burden. IL-17 and the lymphocyte chemokines IP-10, MIG, MIP-1, MIP-1, and RANTES were decreased in the lungs of infected IL-23p19-/- mice when compared to WT. In IL-23p19-/- mice infected with P. carinii, there were fewer effector CD4⁺ T cells in lung tissue. Collectively, these studies indicate that the IL-23/IL-17 axis participates in host defense against P. carinii.

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