Two Types of Interleukin 17A-Producing γδ T Cells in Protection Against Pulmonary Infection With Klebsiella pneumoniae

Abstract

Background: Klebsiella pneumoniae frequently causes life-threatening infection in children. Interleukin 17A (IL-17A) is known to be involved in protection against K. pneumoniae infection through activation of neutrophils.

Methods and results: We found that IL-17A-producing γδ T cells existed more frequently in younger mice on examination of IL-17A-producing lymphocytes in the lung of naive mice at various ages. We hence compared the protective role of IL-17A-producing γδ T cells against pulmonary K. pneumoniae infection in young (3 weeks old) and adult (8-12 weeks old) mice. IL-17A-deficient mice were susceptible to K. pneumonia regardless of age. Cγ-, Vγ4/6-, or Vδ1-deficient mice were susceptible to K. pneumonia at young age, while interleukin 23p19 (IL-23p19)-deficient mice were susceptible at adult age. IL-17A-producing Vγ1^-Vγ4^- γδ T cells expressing canonical Vγ6/Vδ1 genes were dominant over IL-17A-producing Vγ4⁺ γδ T cells in the lungs of young mice after infection. The IL-17A-producing Vγ1^-Vγ4^- γδ T cells expressed an activation marker, CD69, and proliferated in an IL-23-independent manner, while the IL-17A-producing Vγ4⁺ γδ T cells expressing IL-23 receptor but no CD69 proliferated in IL-23-dependent manner.

Conclusions: These results suggest that 2 types of IL-17A-producing γδ T cells are activated for host defense against K. pneumoniae infection by IL-23-dependent or independent mechanism.

Keywords: CD69; IL-17A; IL-23; Klebsiella pneumoniae; Vγ1−Vγ4− γδ T cells; Vγ4 γδ T cells.