Aspergillus fumigatus-induced IL-22 is not restricted to a specific Th cell subset and is dependent on complement receptor 3

J Immunol. 2013 Jun 1;190(11):5629-39. doi: 10.4049/jimmunol.1202601. Epub 2013 May 3.

Abstract

Th cell responses induced by Aspergillus fumigatus have been extensively investigated in mouse models. However, the requirements for differentiation and the characteristics of A. fumigatus-induced human Th cell subsets remain poorly defined. We demonstrate that A. fumigatus induces Th1 and Th17 subsets in human PBMCs. Moreover, we show that the cytokine IL-22 is not restricted to a specific Th subset, in contrast to IL-17A. The pattern recognition and cytokine pathways that skew these Aspergillus-induced Th cell responses are TLR4- and IL-1-, IL-23-, and TNF-α-dependent. These pathways are of specific importance for production of the cytokines IL-17A and IL-22. Additionally, our data reveal that the dectin-1/Syk pathway is redundant and that TLR2 has an inhibitory effect on Aspergillus-induced IL-17A and IL-22 production. Notably, blocking complement receptor (CR)3 significantly reduced Aspergillus-induced Th1 and Th17 responses, and this was independent on the activation of the complement system. CR3 is a known receptor for β-1,3-glucan; however, blocking CR3 had significant effects on Th cell responses induced by heat-killed Aspergillus conidia, which have minimal β-glucan expression on their cell surface. Collectively, these data characterize the human Th cell subsets induced by Aspergillus, demonstrate that the capability to produce IL-22 is not restricted to a specific T cell subset, and provide evidence that CR3 might play a significant role in the adaptive host defense against Aspergillus, although the ligand and its action remain to be elucidated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus fumigatus / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • Humans
  • Inflammation Mediators / immunology
  • Interleukin-22
  • Interleukins / biosynthesis*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lectins, C-Type / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Complement / metabolism*
  • Signal Transduction
  • Syk Kinase
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / metabolism

Substances

  • CLEC7A protein, human
  • Cytokines
  • Inflammation Mediators
  • Interleukins
  • Intracellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • Receptors, Complement
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • Syk protein, mouse