The potential protective role of the combination of IL-22 and TNF-α against genital tract Chlamydia trachomatis infection

Cytokine. 2015 May;73(1):66-73. doi: 10.1016/j.cyto.2015.01.027. Epub 2015 Feb 28.

Abstract

Th22 cells are a novel class of lymphocytes characterized by the secretion of both IL-22 and TNF-α. In summary, Th22 cells have little or no direct impact on other immune cells, but exert selective effects on epithelia. It is not known, however, whether Th22 cells play a role in genital mucosal immunity. Here, we demonstrate that IL-22 and TNF-α synergistically induce several immunomodulatory molecules, such as the antimicrobial peptide mBD-2 (murine β-defensin 2) and the antimicrobial chemokines CXCL-9, -10, and -11 in primary murine oviduct epithelial cells (MOECs). The induction of innate immunity is relevant in an in vitro infection model, in which MOECs stimulated with Th22 cell supernatants or recombinant IL-22 and TNF-α effectively inhibit the growth of Chlamydia trachomatis and maintain the survival of the epithelia compared with IL-22 or TNF-α alone. In summary, we demonstrate that the Th22 cell cytokines IL-22 and TNF-α play important roles in genital tract infection. The potential for Th22 cell cytokines to modulate innate immune mediators may lead to the development of new topical agents to treat and/or prevent immune-mediated sexually transmitted diseases (STDs). In summary, we demonstrate that IL-22 and TNF-α represent a potent, synergistic cytokine combination for inducing genital mucosal immunity.

Keywords: Chemokine; Defensin; IL-22; Oviduct epithelial cell; Th22 cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / metabolism
  • Cell Movement / drug effects
  • Cell Polarity / drug effects
  • Chemokines / metabolism
  • Chlamydia Infections / immunology
  • Chlamydia Infections / microbiology*
  • Chlamydia Infections / prevention & control*
  • Chlamydia trachomatis / drug effects*
  • DNA-Binding Proteins / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Genitalia / drug effects
  • Genitalia / microbiology*
  • Genitalia / pathology
  • HeLa Cells
  • Humans
  • Interleukin-22
  • Interleukins / pharmacology*
  • Mice, Inbred BALB C
  • Oviducts / pathology
  • Receptors, CXCR3 / metabolism
  • Receptors, Interleukin / metabolism
  • STAT3 Transcription Factor / metabolism
  • Th1 Cells / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Up-Regulation / drug effects

Substances

  • Antimicrobial Cationic Peptides
  • Chemokines
  • Cxcr3 protein, mouse
  • DNA-Binding Proteins
  • Interleukins
  • Mbd2 protein, mouse
  • Receptors, CXCR3
  • Receptors, Interleukin
  • STAT3 Transcription Factor
  • Tumor Necrosis Factor-alpha
  • interleukin-22 receptor