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

Andrea Cruz, et al. 2010. J. Exp. Med. 207, 1609-1616

Speaker: Wei-Zhi, Wang (王緯智)                        Time: 15:00~16:00, Nov. 3, 2010

Commentator: Dr. Lien-I Hor (何漣漪老師)       Place: Room 601

Abstract:

Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (M.tb), is one of the main infectious disease in humans. After M.tb infection, immune responses are activated to limit the growth of bacteria and protect the hosts. If uncontrolled it leads to host tissue damage and even death. Nowadays M.bovis bacille Calmette-Guérin (BCG) is the only clinically available vaccine against TB. It has been reported that repeated exposure of Mtb-infected animals to mycobacterial antigens can lead to immune-mediated severe pathology, including necrosis, inflammation and increased granulocyte infiltration. Therefore, the authors studied whether the immunopathological consequences resulting from repeated mycobacterial antigens exposure is mediated by IL-17. C57BL/6 mice infected with M.tb were repeatly injected with BCG to induced lung inflammation. The authors than used this model to investigate the role of IL-17 in the lung lesion. First, the authors demonstrate that repeated BCG exposure mice had a larger number of lung lesions with increased size. In the lung of repeated BCG exposed mice, the inflammatory cytokines TNF-a, IL-6 and MIP-2 were up regulated. The expression of IFN-g was not obviously altered but IL-17 was significantly increased. The authors than examined the role of IL-23 in pathological response by using B6 il23a^-/- mice. Their results showed that the granuloma size and the number of GR1⁺ cells (neutrophil) ingranuloma was decreased in B6 il23a^-/- mice. Finally, the authors demonstrated that the lung pathological response was dependent on IL-17 production by IL-17 neutralization. After treatment with anti–IL-17 antibody, the severity of the lung lesions were reduced in term of the granuloma size and the number of GR1⁺ cell in granulomas. In conclusion, the authors showed that the BCG vaccination induced enhancement of response to M.tb is an IL-17–dependent response. The finding has important implications for the design of vaccines against tuberculosis in the future.

References:

1.      Endogenous IL-17 as a mediator of neutrophil recruitment caused by endotoxin exposure in mouse airways. Miyamoto, et al J. Immunol. 170:4665–4672, 2003.