Pneumocystis murina colonization in immunocompetent surfactant protein A deficient mice following environmental
Michael J Linke1, Alan D Ashbaugh, Jeffery A Demland
1Research Service, Veterans Affairs Medical Center, Cincinnati, OH, USA. michael.linke@va.gov
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.
Conclusion:
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.
Insights
Surfactant protein A (SP-A) protects immunocompetent hosts from Pneumocystis murina colonization. Mice lacking SP-A showed increased susceptibility and transmission of P. murina, highlighting SP-A's crucial role in innate immunity.
Area of Science:
- Immunology
- Infectious Diseases
- Pulmonology
Background:
- Pneumocystis spp. are opportunistic pathogens causing pneumonia in immunocompromised individuals.
- Pneumocystis colonization can occur in immunocompetent hosts and may worsen existing lung conditions.
- Surfactant protein A (SP-A) is an innate immune molecule involved in host defense against Pneumocystis.
Purpose of the Study:
- To investigate the role of SP-A in protecting immunocompetent hosts against Pneumocystis colonization.
- To analyze the susceptibility of SP-A deficient mice to P. murina infection.
Main Methods:
- Comparison of SP-A deficient (KO) and wild-type (WT) immunocompetent mice for P. murina colonization.
- Quantification of P. murina using reverse-transcriptase quantitative PCR (qPCR).
- Measurement of serum antibodies via enzyme-linked immunosorbent assay (ELISA).
Main Results:
- P. murina mRNA was detected only in the lungs of SP-A deficient mice, indicating susceptibility.
- SP-A deficient mice transmitted P. murina to immunodeficient mice.
- Pulmonary cellular response, including CD4+ and CD8+ T-cells, was crucial for colonization clearance, but impaired in SP-A deficient mice.
Conclusions:
- SP-A plays a significant role in protecting immunocompetent hosts from P. murina colonization.
- This study provides a model for investigating Pneumocystis colonization from environmental exposure in humans.
- Maintaining P. murina-free mouse models, even under barrier conditions, presents challenges.
