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Interleukin-17A mediates acquired immunity to pneumococcal colonization
Ying-Jie Lu1, Jane Gross, Debby Bogaert
1Department of Medicine, Division of Infectious Diseases, Children's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America.
Plos Pathogens
|September 20, 2008
Summary
New research reveals that interleukin-17A (IL-17A) is key to clearing pneumococcal colonization in mice and potentially humans. This immune response enhances neutrophil activity, offering a new target for pneumococcal vaccines.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Anticapsular antibodies provide serotype-specific immunity against pneumococci, but children clear colonization before these antibodies develop.
- Previous studies showed CD4+ T cell-dependent, antibody- and serotype-independent protection against pneumococcal colonization after intranasal immunization in mice.
Purpose of the Study:
- To investigate the mechanisms behind antibody-independent pneumococcal immunity.
- To identify the role of specific cytokines and immune cells in accelerated pneumococcal clearance.
Main Methods:
- Intranasal immunization of mice with pneumococci.
- Adoptive transfer of immune CD4+ T cells into RAG1(-/-) mice.
- Analysis of cytokine knockout mice (interferon-gamma, IL-4, IL-17A receptor) and neutrophil-depleted mice.
- In vitro assessment of IL-17A expression and its effect on neutrophil-mediated bacterial killing.
Main Results:
- Immunity accelerates pneumococcal clearance rather than preventing carriage, with neutrophilic infiltration observed.
- Immune CD4+ T cells conferred protection via adoptive transfer.
- IL-17A was critical for protection; mice lacking IL-17A receptor or neutrophils were not protected.
- IL-17A expression was elevated in vaccinated mice and predicted protection.
- IL-17A enhanced pneumococcal killing by human neutrophils, independent of antibodies and complement.
Conclusions:
- Interleukin-17A (IL-17A) plays a critical role in mediating pneumococcal immunity in mice and likely humans.
- IL-17A enhances neutrophil function for bacterial clearance.
- In vitro IL-17A elicitation could inform the development of novel pneumococcal vaccines.
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