Effects of Surfactant Protein-A on the Interaction of Pneumocystis murina with its Host at Different Stages of the Infection in Mice

We examined the effects of surfactant protein A (SP-A), a collectin, on the interaction of Pneumocystis murina with its host at the beginning, early to middle, and late stages of infection. Pneumocystis murina from SP-A wild-type (WT) mice inoculated intractracheally into WT mice (WTS-WTR) adhered well to alveolar macrophages, whereas organisms from SP-A knockout (KO) mice inoculated into KO mice (KOS-KOR) did not. Substitution of WT mice as the source of organisms (WTS-KOR) or recipient host macrophages (KOS-WTR) restored adherence to that found with WTS-WTR mice. In contrast, when immunosuppressed KO and WT mice were inoculated with P. murina from a homologous source (KOS-KOR, WTS-WTR) or heterologous source (WTS-KOR, KOS-WTR) and followed sequentially, WTS-KOR mice had the highest levels of infection at weeks 3 and 4; these mice also had the highest levels of the chemokine macrophage inflammatory protein-2 and neutrophils in lavage fluid at week 3. Surfactant protein-A administered to immunosuppressed KOS-KOR mice with Pneumocystis pneumonia for 8 wk as a therapeutic agent failed to lower the organism burden. We conclude that SP-A can correct the host immune defect in the beginning of P. murina infection, but not in the middle or late stages of the infection.