期刊
JOURNAL OF IMMUNOLOGY
卷 164, 期 5, 页码 2602-2609出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.164.5.2602
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- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P50HL056402, R01HL057011] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL57823, HL57011, 1P50HL56402] Funding Source: Medline
Innate immunity plays an important role in pulmonary host defense against Pneumocystis carinii, an important pathogen in individuals with impaired cell-mediated immunity. We investigated the role of GM-CSF In host defense in a model of P, carinii pneumonia induced by intratracheal inoculation of CD4-depleted mice, Lung GM-CSF levels increased progressively during the infection and were significantly greater than those in uninfected controls 3, 4, and 5 wk after inoculation. When GM-CSF gene-targeted mice (GM(-/-)) depleted of CD4(+) cells were inoculated with P, carinii, the intensities of infection and inflammation were increased significantly compared with those in CD4-depleted mild-type mice. In contrast, transgenic expression of GM-CSF directed solely in the lungs of GM(-/-) mice (using the surfactant protein C promoter) dramatically decreased the intensity of infection and inflammation 4 wk after inoculation. The concentrations of surfactant proteins A and D were greater in both uninfected and infected GM(-/-) mice compared with those in wild-type controls, suggesting that this component of the innate response was preserved in the GM(-/-) mice. However, alveolar macrophages (AM) from GM(-/-) mice demonstrated impaired phagocytosis of purified murine P, carinii organisms in vitro compared with AM from wild-type mice. Similarly, AM production of TNF-alpha in response to P, carinii in vitro was totally absent in AM from GM(-/-) mice,while GM-CSF-replete mice produced abundant TNF in this setting. Thus, GM-CSF plays a critical role in the inflammatory response to P, carinii in the setting of impaired cell-mediated immunity through effects on AM activation.
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