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J Immunol. 2016 Mar 15;196(6):2655-65. doi: 10.4049/jimmunol.1502004. Epub 2016 Feb 10.

Oral Immunization of Mice with Live Pneumocystis murina Protects against Pneumocystis Pneumonia.

Author information

1
Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112;
2
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112; and.
3
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112; and Louisiana Vaccine Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112.
4
Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112; Louisiana Vaccine Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112.
5
Section of Pulmonary/Critical Care and Allergy/Immunology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112; dwelsh@lsuhsc.edu.

Abstract

Pneumocystis pneumonia is a major cause of morbidity and mortality in immunocompromised patients, particularly those infected with HIV. In this study, we evaluated the potential of oral immunization with live Pneumocystis to elicit protection against respiratory infection with Pneumocystis murina. C57BL/6 mice vaccinated with live P. murina using a prime-boost vaccination strategy were protected from a subsequent lung challenge with P. murina at 2, 7, 14, and 28 d postinfection even after CD4(+) T cell depletion. Specifically, vaccinated immunocompetent mice had significantly faster clearance than unvaccinated immunocompetent mice and unvaccinated CD4-depleted mice remained persistently infected with P. murina. Vaccination also increased numbers of CD4(+) T cells, CD8(+) T cells, CD19(+) B cells, and CD11b(+) macrophages in the lungs following respiratory infection. In addition, levels of lung, serum, and fecal P. murina-specific IgG and IgA were increased in vaccinated animals. Furthermore, administration of serum from vaccinated mice significantly reduced Pneumocystis lung burden in infected animals compared with control serum. We also found that the diversity of the intestinal microbial community was altered by oral immunization with P. murina. To our knowledge, our data demonstrate for the first time that an oral vaccination strategy prevents Pneumocystis infection.

PMID:
26864029
PMCID:
PMC4779750
DOI:
10.4049/jimmunol.1502004
[Indexed for MEDLINE]
Free PMC Article

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