Role of Type I IFNs in Pulmonary Complications of Pneumocystis murina Infection

  • Meissner N
  • Swain S
  • Tighe M
  • et al.
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Despite the advent of highly active antiretroviral therapy, pulmonary complications in AIDS are a common clinical problem. Pneumocystis jiroveci infection causes a life-threatening pneumonia, especially in individuals with CD4 T cell deficiencies as occurs in AIDS. Although Pneumocystis sp. is an extracellular fungal pathogen, CD8 T cells are the predominant lymphocyte recruited to the lung in CD4-deficient humans and mice during Pneumocystis pneumonia, and we have found that these CD8 T cells are responsible for subsequent lung damage in CD4 T cell-depleted mice. Comparing CD4 T cell-depleted IFN-alpha receptor knockout (KO) mice to wild-type mice, we found that this CD8 T cell recruitment and lung damage is type I IFN (IFN-alphabeta) dependent. However, in both CD4 competent, wild-type and IFN-alpha receptor (IFNAR) KO mice, Pneumocystis infection leads to an eosinophilic granulocyte influx with bronchial epithelial changes as seen in asthma. This response is delayed in IFNAR KO mice, as is pathogen clearance. Although the inflammation is transient in wild-type animals and resolves upon Pneumocystis clearance, it is more severe and persists through day 35 postinfection in IFNAR KO mice, leading to fibrosis. In addition, IFNAR KO, but not wild-type, mice mount a Pneumocystis-specific IgE response, an indicator of allergic sensitization. Thus, in the absence of IFNAR signaling and CD4 T cells, Pneumocystis-mediated lung damage does not occur, whereas in CD4-competent animals, the absence of IFNAR signaling results in an exacerbated Th2 response, asthma-like symptoms, and fibrosis. Therefore, both CD4 T cell- and type I IFN-mediated mechanisms can determine pulmonary complications from Pneumocystis infection.




Meissner, N. N., Swain, S., Tighe, M., Harmsen, A., & Harmsen, A. (2005). Role of Type I IFNs in Pulmonary Complications of Pneumocystis murina Infection . The Journal of Immunology, 174(9), 5462–5471.

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