期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 207, 期 8, 页码 1609-1616出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20100265
关键词
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资金
- Fundacao para a Ciencia e Tecnologia [SFRH/BPD/33036/2007, SFRH/BD/15911/2005]
- Health Service of Fundacao Calouste Gulbenkian and Fundacao para a Ciencia e Tecnologia [PTDC/SAU-MII/70895/2006]
- National Institutes of Health [HL69409, AI072689, AI61511, AI46535, AI69121, AI67723]
- American Lung Association
- Trudeau Institute
- Fundação para a Ciência e a Tecnologia [SFRH/BD/15911/2005, PTDC/SAU-MII/70895/2006] Funding Source: FCT
Infection usually leads to the development of acquired immune responses associated with clearance or control of the infecting organism. However, if not adequately regulated, immune-mediated pathology can result. Tuberculosis is a worldwide threat, and development of an effective vaccine requires that the protective immune response to Mycobacterium tuberculosis (Mtb) be dissected from the pathological immune response. This distinction is particularly important if new vaccines are to be delivered to Mtb-exposed individuals, as repeated antigenic exposure can lead to pathological complications. Using a model wherein mice are vaccinated with bacille Calmette-Guerin after Mtb infection, we show that repeated vaccination results in increased IL-17, tumor necrosis factor, IL-6, and MIP-2 expression, influx of granulocytes/neutrophils, and lung tissue damage. This pathological response is abrogated in mice deficient in the gene encoding IL-23p19 or in the presence of IL-17-blocking antibody. This finding that repeated exposure to mycobacterial antigen promotes enhanced IL-17-dependent pathological consequences has important implications for the design of effective vaccines against Mtb.
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