Pathological role of interleukin 17 in mice subjected to repeated BCG vaccination after infection with Mycobacterium tuberculosis

• Author(s): Cruz, Andrea ; Fraga, Alexandra G. ; Fountain, Jeffrey J. ; Rangel-Moreno, Javier ; Torrado, Egídio ; Saraiva, Margarida ; Pereira, Daniela Maria Ramos ; Randall, Troy D. ; Pedrosa, Jorge ; Cooper, Andrea M. ; Castro, António G.
• Date: 2010
• Persistent ID: http://hdl.handle.net/1822/29615
• Origin: RepositóriUM - Universidade do Minho
• Subject(s): Science & Technology
• Document Type: Journal article
• Language: English
• Contributor(s): Universidade do Minho

Description

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-Guérin 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.

A. Cruz and A.G. Fraga were supported by the Fundacao para a Ciencia e Tecnologia (grants SFRH/BPD/33036/2007 and SFRH/BD/15911/2005). Other funding came from the Health Service of Fundacao Calouste Gulbenkian and Fundacao para a Ciencia e Tecnologia (grant PTDC/SAU-MII/70895/2006), the National Institutes of Health (grants HL69409, AI072689, and AI61511 to T. D. Randall; and grants AI46535, AI69121, and AI67723), the American Lung Association DeSouza Award, and Trudeau Institute funding to A.M. Cooper.