Surfactant protein A limits Pneumocystis murina infection in immunosuppressed C3H/HeN mice and modulates host response during infection.
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.
Linke
Michael
M
Department of Veterans Affairs Medical Center, Research Service, 3200 Vine Street, Cincinnati, OH 45220, USA. Michael.Linke@med.va.gov
Ashbaugh
Alan
A
Koch
Judith
J
Tanaka
Reiko
R
Walzer
Peter
P
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*
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D037662:Pulmonary Surfactant-Associated Protein A