Interleukin-7 protects against bacterial respiratory infection by promoting IL-17A-producing innate T-cell response

Mucosal Immunol. 2020 Jan;13(1):128-139. doi: 10.1038/s41385-019-0212-y. Epub 2019 Oct 18.

Abstract

Interleukin-7 (IL-7) is a critical cytokine in B- and T-lymphocyte development and maturation. Recent evidence suggests that IL-7 is a preferential homeostatic and survival factor for RORγt+ innate T cells such as natural killer T (NKT) cells, γδT cells, and mucosal-associated invariant T (MAIT) cells in the periphery. Given the important contribution of these populations in antibacterial immunity at barrier sites, we questioned whether IL-7 could be instrumental in boosting the local host immune response against respiratory bacterial infection. By using a cytokine-monoclonal antibody approach, we illustrated a role for topical IL-7 delivery in increasing the pool of RORγt+ IL-17A-producing innate T cells. Prophylactic IL-7 treatment prior to Streptococcus pneumoniae infection led to better bacterial containment, a process associated with increased neutrophilia and that depended on γδT cells and IL-17A. Last, combined delivery of IL-7 and α-galactosylceramide (α-GalCer), a potent agonist for invariant NKT (iNKT) cells, conferred an almost total protection in terms of survival, an effect associated with enhanced IL-17 production by innate T cells and neutrophilia. Collectively, we provide a proof of concept that IL-7 enables fine-tuning of innate T- cell functions. This might pave the way for considering IL-7 as an innovative biotherapeutic against bacterial infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / metabolism
  • Cells, Cultured
  • Galactosylceramides / immunology
  • Humans
  • Immunity, Innate
  • Immunotherapy / methods*
  • Interleukin-17 / metabolism*
  • Interleukin-7 / administration & dosage
  • Interleukin-7 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism*
  • Neutrophils / immunology*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Pneumococcal Infections / immunology*
  • Respiratory Tract Infections / immunology*
  • Streptococcus pneumoniae / physiology*

Substances

  • Antibodies, Blocking
  • Galactosylceramides
  • Interleukin-17
  • Interleukin-7
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • alpha-galactosylceramide