Nitric oxide and host defense against Pneumocystis carinii infection in a mouse model

Abstract

To investigate whether successful host defense against Pneumocystis carinii is dependent on induction of inducible nitric oxide synthase (iNOS) in alveolar macrophages, immunocompetent mice, mice depleted of CD4 lymphocytes with anti-CD4 antibody, and mice with severe combined immunodeficiency (scid) were inoculated intratracheally with P. carinii. Three weeks later, immunocompetent mice had cleared the organisms completely, while CD4 cell-depleted and scid mice were severely infected (scores, 3.6 +/- 0.2 and 2.8 +/- 0.2, respectively). Inflammation scores were significantly higher in CD4 cell-depleted mice (3.4 +/- 0.2) than in scid mice (0.6 +/- 0.2). Minimal iNOS mRNA was detectable in lung tissue from immunocompetent mice; iNOS mRNA was comparable in scid mice and mice inoculated with PBS but was 6-fold higher in CD4 cell-depleted mice. Immunohistochemistry localized iNOS protein to alveolar macrophages in CD4 cell-depleted mice. Thus, iNOS is an unlikely participant in host defense against P. carinii, because enzyme expression does not correlate with either clearance or severity of infection.