Abstract
BackgroundPneumocystis 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.MethodsTo 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).ResultsDetection 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.ConclusionThese 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.
Highlights
Pneumocystis spp. are opportunistic pathogens that cause pneumonia in immunocompromised humans and animals
These data support an important role for surfactant protein A (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
Environmental exposure to P. murina leads to the development of a transient colonization in immunocompetent KO mice Immunocompetent WT and KO mice, between the ages of 2–18 weeks, with no experimental exposure to P. murina were examined for P. murina colonization by testing for the presence of large mitochondrial ribosomal RNA gene (mtLSU) message by RT-quantitative polymerase chain reaction (PCR) (qPCR)
Summary
Pneumocystis spp. are opportunistic pathogens that cause pneumonia in immunocompromised humans and animals. The source of Pneumocystis infection in humans and animals remains unknown, but it has been proposed that persons with colonized with P. jirovecii may act as a reservoir of infection and as a source of infectious organisms [3,4]. Results from both human and animal studies demonstrate that colonization with Pneumocystis is not a rare event and may lead to worsening of other pulmonary conditions [5,6,7,8,9]. Cigarette smoking and certain locations of residence demonstrate a positive correlation with the incidence of P. jirovecii colonization [7]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call