Effects of surfactant protein-A on the interaction of Pneumocystis murina with its host at different stages of the infection in mice

Abstract

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 (WT(S)-WT(R)) adhered well to alveolar macrophages, whereas organisms from SP-A knockout (KO) mice inoculated into KO mice (KO(S)-KO(R)) did not. Substitution of WT mice as the source of organisms (WT(S)-KO(R)) or recipient host macrophages (KO(S)-WT(R)) restored adherence to that found with WT(S)-WT(R) mice. In contrast, when immunosuppressed KO and WT mice were inoculated with P. murina from a homologous source (KO(S)-KO(R), WT(S)-WT(R)) or heterologous source (WT(S)-KO(R), KO(S)-WT(R)) and followed sequentially, WT(S)-KO(R) 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 KO(S)-KO(R) 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.

Fig. 1

Adherence of Pneumocystis murina to alveolar macrophages in vivo in KO and WT mice after intratracheal (IT) inoculation of P. murina. Data are presented as mean ± SEM % macrophages with ≥ 1 P. murina organism attached to them. There were 5 animals/group. Between group comparisons: ¹ p < 0.05, ² p < 0.01, ³ p < 0.001.

Fig. 2

Sequential development of Pneumocystis murina infection in immunosuppressed KO and WT mice 2A. After intratracheal (IT) inoculation of P. murina obtained from KO and WT mice. Data are presented as mean ± SEM log₁₀ cyst counts/lung in each mouse group. There were about 10 mice per group at each time point. Within group comparisons: ^a p < 0.05, ^b p < 0.01, ^c p < 0.001. Between group comparisons: ¹ p < 0.05, ² p < 0.01, ³ p < 0.001. 2B. Development at 4 weeks after direct exposure to KO and WT mice with active PCP. Data are presented as mean ± SEM log₁₀ cyst counts/lung in each mouse group. There were 4 to 6 mice per group at each time point. Between group comparisons: ¹ p < 0.05, ² p < 0.01, ³ p < 0.001.

Fig. 3

Development of Pneumocystis murina infection in immunosuppressed KO mice inoculated intratracheally with P. murina and administered 100 µg SP-A (SP-A group) intranasally or placebo (control group) 3 times/week for 8 wk. There were 14 mice/group. Between group comparisons: ¹ p < 0.05, ² p < 0.01, ³ p < 0.001.