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

作者：Cruz Andrea; Fraga Alexandra G; Fountain Jeffrey J; Rangel Moreno Javier; Torrado Egidio; Saraiva Margarida; Pereira Daniela R; Randall Troy D; Pedrosa Jorge; Cooper Andrea M; Castro Antonio G^*

来源：Journal of Experimental Medicine, 2010, 207(8): 1609-1616.

DOI：10.1084/jem.20100265

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.

• 出版日期2010-8-2