Cytokine modulation alters pulmonary clearance of Rhodococcus equi and development of granulomatous pneumonia.
Rhodococcus equi, a facultative intracellular bacterium, causes chronic, often fatal granulomatous pneumonia in young horses and in humans with AIDS. The inability of host alveolar macrophages to kill intracellular R. equi results in the development of granulomas and progressive loss of pulmonary parenchyma. Clearance of the organism from the lung requires functional CD4+ T cells. The purpose of this study was to identify the cytokine effector mechanisms that mediate clearance of R. equi from the lung. Mice were treated with monoclonal antibodies (MAbs) to either gamma interferon (IFN-gamma) or interleukin-4 (IL-4) to determine the role of endogenous production of these cytokines in pulmonary clearance of R. equi. Mice treated with an anti-IL-4 or isotype control MAb cleared R. equi by 21 days postinfection and expressed increased levels of IFN-gamma mRNA, as detected by transcriptional analysis of bronchial lymph node CD4+ T cells. In contrast, mice treated with the anti-IFN-gamma MAb failed to express detectable IFN-gamma mRNA, expressed increased levels of IL-4 mRNA, failed to clear pulmonary infection, and developed pulmonary granulomas with large numbers of eosinophils. The enhancement of IL-4 mRNA expression and a predominance of eosinophils in pulmonary lesions of anti-IFN-gamma-treated mice suggest that a nonprotective Th2 response in involved in disease pathogenesis. The association of increased bronchial lymph node CD4+ T-cell IFN-gamma mRNA expression with pulmonary clearance of R. equi suggests that a Th1 response is protective.
Kanaly
S T
ST
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040, USA.
Hines
S A
SA
Palmer
G H
GH
D000193:Actinomycetales Infections / Q000276:immunology*; D000818:Animals; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology*; D012333:RNA, Messenger / Q000235:genetics; D016929:Rhodococcus equi / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma