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Interleukin-17A mediates acquired immunity to pneumococcal colonization.

Ying-Jie Lu1, Jane Gross, Debby Bogaert

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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.

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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.