| Innate immune activation by the viral PAMP poly I:C potentiates pulmonary graft-versus-host disease after allogeneic hematopoietic cell transplant. | |
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MedLine Citation:
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PMID: 21070856 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Respiratory viral infections cause significant morbidity and increase the risk for chronic pulmonary graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT). Our overall hypothesis is that local innate immune activation potentiates adaptive alloimmunity. In this study, we hypothesized that a viral pathogen-associated molecular pattern (PAMP) alone can potentiate pulmonary GVHD after allogeneic HCT. We, therefore, examined the effect of pulmonary exposure to polyinosinic:polycytidylic acid (poly I:C), a viral mimetic that activates innate immunity, in an established murine HCT model. Poly I:C-induced a marked pulmonary T cell response in allogeneic HCT mice as compared to syngeneic HCT, with increased CD4+ cells in the lung fluid and tissue. This lymphocytic inflammation persisted at 2 weeks post poly I:C exposure in allogeneic mice and was associated with CD3+ cell infiltration into the bronchiolar epithelium and features of epithelial injury. In vitro, poly I:C enhanced allospecific proliferation in a mixed lymphocyte reaction. In vivo, poly I:C exposure was associated with an early increase in pulmonary monocyte recruitment and activation as well as a decrease in CD4+FOXP3+ regulatory T cells in allogeneic mice as compared to syngeneic. In contrast, intrapulmonary poly I:C did not alter the extent of systemic GVHD in either syngeneic or allogeneic mice. Collectively, our results suggest that local activation of pulmonary innate immunity by a viral molecular pattern represents a novel pathway that contributes to pulmonary GVHD after allogeneic HCT, through a mechanism that includes increased recruitment and maturation of intrapulmonary monocytes. |
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Authors:
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Christine V Kinnier; Tereza Martinu; Kymberly M Gowdy; Julia L Nugent; Francine L Kelly; Scott M Palmer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-09 |
Journal Detail:
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Title: Transplant immunology Volume: 24 ISSN: 1878-5492 ISO Abbreviation: Transpl. Immunol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-27 Completed Date: 2011-07-07 Revised Date: 2012-05-10 |
Medline Journal Info:
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Nlm Unique ID: 9309923 Medline TA: Transpl Immunol Country: England |
Other Details:
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Languages: eng Pagination: 83-93 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Medicine, Duke University Medical Center, 106 Research Drive, Building MSRB2 Room 2100B, Durham, NC 27710, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptive Immunity Animals Antigens, CD3 CD4-Positive T-Lymphocytes / immunology Flow Cytometry Graft vs Host Disease / immunology* Hematopoietic Stem Cell Transplantation* Immunity, Innate* Lung / immunology* Lung Diseases / immunology* Mice Mice, Inbred C57BL Monocytes / immunology* Monocytes, Activated Killer / immunology Poly I-C / immunology* Respiratory Mucosa / immunology Respiratory Tract Infections / virology T-Lymphocytes, Regulatory / immunology Transplantation, Homologous |
| Grant Support | |
ID/Acronym/Agency:
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1 K24 HL091140/HL/NHLBI NIH HHS; 1P50-HL084917-011/HL/NHLBI NIH HHS; K24 HL091140/HL/NHLBI NIH HHS; K24 HL091140-01A1/HL/NHLBI NIH HHS; K24 HL091140-02/HL/NHLBI NIH HHS; K24 HL091140-04/HL/NHLBI NIH HHS; KL2 RR024127-03/RR/NCRR NIH HHS; P50 HL084917-01/HL/NHLBI NIH HHS; P50 HL084917-02/HL/NHLBI NIH HHS; P50 HL084917-03/HL/NHLBI NIH HHS; P50 HL084917-04/HL/NHLBI NIH HHS; RR024 127-03/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD3; 24939-03-5/Poly I-C |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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