Kinetics of the Immune Response Profile in Guinea Pigs after Vaccination withMycobacterium bovisBCG and Infection withMycobacterium tuberculosis
| Autor: | Jennifer L. Taylor, Ajay Grover, Andrew Keyser, Kimberly Arnett, Linda Izzo, JoLynn Troudt, Angelo Izzo, Drew A. Rholl |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Tuberculosis
T-Lymphocytes medicine.medical_treatment Guinea Pigs Immunology Microbiology Mycobacterium tuberculosis Immune system Immunity medicine Animals Host Response and Inflammation Mycobacterium bovis biology Reverse Transcriptase Polymerase Chain Reaction Flow Cytometry medicine.disease biology.organism_classification Vaccination Infectious Diseases Cytokine BCG Vaccine Cytokines Female Parasitology CD8 |
| Zdroj: | Infection and Immunity. 77:4837-4846 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | The guinea pig model of tuberculosis is used extensively in assessing novel vaccines, sinceMycobacterium bovisBCG vaccination effectively prolongs survival after low-dose aerosol infection with virulentM. tuberculosis. To better understand how BCG extends time to death after pulmonary infection withM. tuberculosis, we examined cytokine responses postvaccination and recruitment of activated T cells and cytokine response postinfection. At 10 weeks postvaccination, splenic gamma interferon (IFN-γ) mRNA was significantly elevated compared to the levels at 5 weeks in ex vivo stimulation assays. At 15, 40, 60, and 120 days postinfection, T-cell activation (CD4+CD62Llowand CD8+CD62Llow) and mRNA expression of IFN-γ, tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-10, IL-12, and eomesodermin were assessed. Our data show that at day 40, BCG-vaccinated guinea pigs had significantly increased levels of IFN-γ mRNA expression but decreased TNF-α mRNA expression in their lungs compared to the levels in nonvaccinated animals. At day 120, a time when nonvaccinated guinea pigs succumbed to infection, low levels of IFN-γ mRNA were observed even though there were increasing levels of IL-1, IL-12, and IL-10, and the numbers of activated T cells did not differ from those in BCG-vaccinated animals. BCG vaccination conferred the advantage of recruiting greater numbers of CD4+CD62LlowT cells at day 40, although the numbers of CD8+CD62LlowT cells were not elevated compared to the numbers in nonvaccinated animals. Our data suggest that day 40 postinfection may be a pivotal time point in determining vaccine efficacy and prolonged survival and that BCG promotes the capacity of T cells in the lungs to respond to infection. |
| Databáze: | OpenAIRE |
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