Pneumocystis murina colonization in immunocompetent surfactant protein A deficient mice following environmental exposure.
BACKGROUND
Pneumocystis spp. are opportunistic pathogens that cause pneumonia in immunocompromised humans and animals. Pneumocystis colonization has also been detected in immunocompetent hosts and may exacerbate other pulmonary diseases. Surfactant protein A (SP-A) is an innate host defense molecule and plays a role in the host response to Pneumocystis.


METHODS
To analyze the role of SP-A in protecting the immunocompetent host from Pneumocystis colonization, the susceptibility of immunocompetent mice deficient in SP-A (KO) and wild-type (WT) mice to P. murina colonization was analyzed by reverse-transcriptase quantitative PCR (qPCR) and serum antibodies were measured by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Detection of P. murina specific serum antibodies in immunocompetent WT and KO mice indicated that the both strains of mice had been exposed to P. murina within the animal facility. However, P. murina mRNA was only detected by qPCR in the lungs of the KO mice. The incidence and level of the mRNA expression peaked at 8-10 weeks and declined to undetectable levels by 16-18 weeks. When the mice were immunosuppressed, P. murina cyst forms were also only detected in KO mice. P. murina mRNA was detected in SCID mice that had been exposed to KO mice, demonstrating that the immunocompetent KO mice are capable of transmitting the infection to immunodeficient mice. The pulmonary cellular response appeared to be responsible for the clearance of the colonization. More CD4+ and CD8+ T-cells were recovered from the lungs of immunocompetent KO mice than from WT mice, and the colonization in KO mice depleted CD4+ cells was not cleared.


CONCLUSIONS
These data support an important role for SP-A in protecting the immunocompetent host from P. murina colonization, and provide a model to study Pneumocystis colonization acquired via environmental exposure in humans. The results also illustrate the difficulties in keeping mice from exposure to P. murina even when housed under barrier conditions.
Linke
Michael J
MJ
Research Service, Veterans Affairs Medical Center, Cincinnati, OH, USA. michael.linke@va.gov
Ashbaugh
Alan D
AD
Demland
Jeffery A
JA
Walzer
Peter D
PD
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D004781:Environmental Exposure; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D007121:Immunocompetence / Q000187:drug effects / Q000235:genetics; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D016513:Mice, SCID; D011010:Pneumocystis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D011020:Pneumonia, Pneumocystis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control* / Q000635:transmission; D037662:Pulmonary Surfactant-Associated Protein A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012331:RNA, Fungal / Q000097:blood; D012333:RNA, Messenger / Q000097:blood; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D000908:Antibodies, Fungal; D007166:Immunosuppressive Agents; D037662:Pulmonary Surfactant-Associated Protein A; D012331:RNA, Fungal; D012333:RNA, Messenger