α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice

Blood. 2015 May 7;125(19):3014-23. doi: 10.1182/blood-2014-12-615781. Epub 2015 Mar 4.

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for various hematopoietic disorders. Graft-versus-host disease (GVHD) and infections are the major obstacles of HSCT, and their close relationship has been suggested. Although roles of bacterial and viral infections in the pathophysiology of GVHD are well described, impacts of fungal infection on GVHD remain to be elucidated. In mouse models of GVHD, injection of α-mannan (Mn), a major component of fungal cell wall, or heat-killed Candida albicans exacerbated GVHD, particularly in the lung. Mn-induced donor T-cell polarization toward Th17 and lung-specific chemokine environment in GVHD led to accumulation of Th17 cells in the lung. The detrimental effects of Mn on GVHD depended on donor IL-17A production and host C-type lectin receptor Dectin-2. These results suggest a previously unrecognized link between pulmonary GVHD and fungal infection after allogeneic HSCT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Marrow Transplantation / adverse effects*
  • Candida albicans / physiology
  • Candidiasis / immunology
  • Candidiasis / microbiology
  • Candidiasis / pathology
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • Interferon-gamma / metabolism
  • Interleukin-17 / physiology*
  • Lung Diseases / etiology*
  • Lung Diseases / mortality
  • Lung Diseases / pathology
  • Lymphocyte Activation
  • Mannans / adverse effects*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Th17 Cells / immunology*
  • Transplantation, Homologous

Substances

  • Interleukin-17
  • Mannans
  • RNA, Messenger
  • Interferon-gamma