α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice.
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.
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
Hidetaka
H
Uryu
Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
Daigo
http://orcid.org/0000-0001-9489-9704
D
Hashimoto
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
Koji
K
Kato
Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
Eiko
E
Hayase
Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
Satomi
S
Matsuoka
Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
Reiki
R
Ogasawara
Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
Shuichiro
S
Takahashi
Department of Hematology and Oncology, University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan;
Yoshinobu
Y
Maeda
Center for Cellular and Molecular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
Hiromi
H
Iwasaki
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
Toshihiro
T
Miyamoto
Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan;
Shinobu
S
Saijo
Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan; and.
Yoichiro
Y
Iwakura
Queensland Institute of Medical Research, Brisbane, Australia.
Geoffrey R
GR
Hill
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; Center for Cellular and Molecular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan;
Koichi
K
Akashi
Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
Takanori
T
Teshima
D000818:Animals; D015153:Blotting, Western; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002176:Candida albicans / Q000502:physiology; D002177:Candidiasis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000502:physiology*; D008171:Lung Diseases / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D008213:Lymphocyte Activation; D008351:Mannans / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D058504:Th17 Cells / Q000276:immunology*; D014184:Transplantation, Homologous
D020381:Interleukin-17; D008351:Mannans; D012333:RNA, Messenger; D007371:Interferon-gamma