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Innate immune activation by the viral PAMP poly I:C potentiates pulmonary graft-versus-host disease after allogeneic hematopoietic cell transplant.
- Source :
-
Transplant immunology [Transpl Immunol] 2011 Jan 15; Vol. 24 (2), pp. 83-93. Date of Electronic Publication: 2010 Nov 09. - Publication Year :
- 2011
-
Abstract
- 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.<br /> (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Subjects :
- Adaptive Immunity
Animals
CD3 Complex
CD4-Positive T-Lymphocytes immunology
Flow Cytometry
Mice
Mice, Inbred C57BL
Monocytes, Activated Killer immunology
Respiratory Mucosa immunology
Respiratory Tract Infections virology
T-Lymphocytes, Regulatory immunology
Transplantation, Homologous
Graft vs Host Disease immunology
Hematopoietic Stem Cell Transplantation
Immunity, Innate
Lung immunology
Lung Diseases immunology
Monocytes immunology
Poly I-C immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5492
- Volume :
- 24
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Transplant immunology
- Publication Type :
- Academic Journal
- Accession number :
- 21070856
- Full Text :
- https://doi.org/10.1016/j.trim.2010.11.004