IL-10 modulates host responses and lung damage induced by Pneumocystis carinii infection

Mahboob H. Qureshi, Allen G. Harmsen, Beth A. Garvy

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Host responses to Pneumocystis carinii infection mediate impairment of pulmonary function and contribute to the pathogenesis of pneumonia. IL-10 is known to inhibit inflammation and reduce the severity of pathology caused by a number of infectious organisms. In the present studies, IL-10-deficient (IL-10 knockout (KO)) mice were infected with P. carinii to determine whether the severity of pathogenesis and the efficiency of clearance of the organisms could be altered in the absence of IL-10. The clearance kinetics of P. carinii from IL-10 KO mice was significantly enhanced compared with that of wild-type (WT) mice. This corresponded to a more intense CD4+ and CD8+ T cell response as well as an earlier neutrophil response in the lungs of IL-10 KO mice. Furthermore, IL-12, IL-18, and IFN-γ were found in the bronchoalveolar lavage fluids at earlier time points in IL-10 KO mice suggesting that alveolar macrophages were activated earlier than in WT mice. However, when CD4+ cells were depleted from P. carinii-infected IL-10 KO mice, the ability to enhance clearance was lost. Furthermore, CD4-depleted IL-10 KO mice had significantly more lung injury than CD4-depleted WT mice even though the intensity of the inflammatory responses was similar. This was characterized by increased vascular leakage, decreased oxygenation, and decreased arterial pH. These data indicate that IL-10 down-regulates the immune response to P. carinii in WT mice; however, in the absence of CD4+ T cells, IL-10 plays a critical role in controlling lung damage independent of modulating the inflammatory response.

Original languageEnglish
Pages (from-to)1002-1009
Number of pages8
JournalJournal of Immunology
Volume170
Issue number2
DOIs
StatePublished - Jan 15 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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