title: Surfactant protein A limits Pneumocystis murina infection in immunosuppressed C3H/HeN mice and modulates host response during infection.
abstract: The development of Pneumocystis murina pneumonia and host response were characterized over time and at different levels of infection in corticosteroid immunosuppressed surfactant protein A (SP-A) knockout and wild-type (WT) mice. Infection increased over time in both strains of mice; however, significantly more cyst forms were detected in the knockout mice at intermediate and late stages of infection. In mice with heavy infections, TNF-alpha and IFN-gamma protein concentrations were significantly higher in pulmonary lavage fluid from knockout mice. There was a significant positive correlation between TNF-alpha and IFN-gamma concentrations and the level of infection in knockout mice, but not in WT mice. No significant differences were detected in IL-1 levels between the two strains of mice at any of the time points or at any level of infection. At heavier infection levels, significantly more MIP-2 protein was detected in the lungs of knockout mice, but a significant positive correlation between MIP-2 concentrations and the infection level was detected in both groups of mice. At the intermediate stage of infection, a significantly higher percentage of neutrophils was detected in the lungs of knockout mice than in WT mice. There was no difference in SP-D levels between WT and KO mice with identical levels of infection. These data support a protective role for SP-A in host defense against Pneumocystis and suggest that the effects of SP-A on the host response vary based on the intensity of the infection.
authors.affiliation: Department of Veterans Affairs Medical Center, Research Service, 3200 Vine Street, Cincinnati, OH 45220, USA. Michael.Linke@med.va.gov
authors.forename: Michael
authors.initials: M
authors.lastname: Linke
authors.forename: Alan
authors.initials: A
authors.lastname: Ashbaugh
authors.forename: Judith
authors.initials: J
authors.lastname: Koch
authors.forename: Reiko
authors.initials: R
authors.lastname: Tanaka
authors.forename: Peter
authors.initials: P
authors.lastname: Walzer
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D011010:Pneumocystis / Q000302:isolation & purification / Q000472:pathogenicity*; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*
chemical_list: D000305:Adrenal Cortex Hormones; D016207:Cytokines; D037662:Pulmonary Surfactant-Associated Protein A