tetano
Editor, Senior Moderator
Am J Pathol. 2013 Oct 31. pii: S0002-9440(13)00667-6. doi: 10.1016/j.ajpath.2013.09.012. [Epub ahead of print]
Mucosal Pre-Exposure to Th17-Inducing Adjuvants Exacerbates Pathology after Influenza Infection.
Gopal R, Rangel-Moreno J, Fallert Junecko BA, Mallon DJ, Chen K, Pociask DA, Connell TD, Reinhart TA, Alcorn JF, Ross TM, Kolls JK, Khader SA.
Source
Division of Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Abstract
Mucosal vaccines are thought to confer superior protection against mucosal infectious diseases. In addition, mucosal routes of vaccine delivery preferentially induce the generation of T helper 17 (Th17) cells, which produce the cytokine IL-17. Th17 cells are critical in mediating vaccine-induced immunity against several mucosal infectious diseases. However, IL-17 is also a potent proinflammatory cytokine, and we recently showed that IL-17 mediates immunopathology and lung injury after influenza infection in mice. In the present study, we tested the hypothesis that mucosal pre-exposure to Th17-inducing adjuvants can promote disease exacerbation upon subsequent infection with influenza virus. Mice mucosally pre-exposed to Th17-inducing adjuvants, such as type II heat-labile enterotoxin or cholera toxin, resulted in increased morbidity and exacerbated lung inflammation upon subsequent infection with influenza virus. Furthermore, the increased morbidity was accompanied by increased expression of inflammatory chemokines and increased accumulation of neutrophils. Importantly, blockade of the IL-17 pathway in mice pre-exposed to Th17-inducing adjuvants resulted in attenuation of the inflammatory phenotype seen in influenza-infected mice. Our findings indicate that, before mucosal Th17-inducing adjuvants can be used in vaccine strategies, the short- and long-term detrimental effects of such adjuvants on disease exacerbation and lung injury in response to infections, such as influenza, should be carefully studied.
Copyright ? 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
PMID:
24183780
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24183780
Mucosal Pre-Exposure to Th17-Inducing Adjuvants Exacerbates Pathology after Influenza Infection.
Gopal R, Rangel-Moreno J, Fallert Junecko BA, Mallon DJ, Chen K, Pociask DA, Connell TD, Reinhart TA, Alcorn JF, Ross TM, Kolls JK, Khader SA.
Source
Division of Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Abstract
Mucosal vaccines are thought to confer superior protection against mucosal infectious diseases. In addition, mucosal routes of vaccine delivery preferentially induce the generation of T helper 17 (Th17) cells, which produce the cytokine IL-17. Th17 cells are critical in mediating vaccine-induced immunity against several mucosal infectious diseases. However, IL-17 is also a potent proinflammatory cytokine, and we recently showed that IL-17 mediates immunopathology and lung injury after influenza infection in mice. In the present study, we tested the hypothesis that mucosal pre-exposure to Th17-inducing adjuvants can promote disease exacerbation upon subsequent infection with influenza virus. Mice mucosally pre-exposed to Th17-inducing adjuvants, such as type II heat-labile enterotoxin or cholera toxin, resulted in increased morbidity and exacerbated lung inflammation upon subsequent infection with influenza virus. Furthermore, the increased morbidity was accompanied by increased expression of inflammatory chemokines and increased accumulation of neutrophils. Importantly, blockade of the IL-17 pathway in mice pre-exposed to Th17-inducing adjuvants resulted in attenuation of the inflammatory phenotype seen in influenza-infected mice. Our findings indicate that, before mucosal Th17-inducing adjuvants can be used in vaccine strategies, the short- and long-term detrimental effects of such adjuvants on disease exacerbation and lung injury in response to infections, such as influenza, should be carefully studied.
Copyright ? 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
PMID:
24183780
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24183780