Mycobacterium bovisBCG-Specific Th17 Cells Confer Partial Protection againstMycobacterium tuberculosisInfection in the Absence of Gamma Interferon

Infection and Immunity - Tập 78 Số 10 - Trang 4187-4194 - 2010
Teresa M. Wozniak1, Bernadette M. Saunders2,1, Anthony A. Ryan1, Warwick J. Britton2,1
1Mycobacterial Research Program, Centenary Institute, Locked Bag No. 6, Newtown, NSW 2042
2Discipline of Medicine, Central Clinical School, University of Sydney, Sydney, NSW 2006, Australia

Tóm tắt

ABSTRACTProtective immunity against tuberculosis (TB) requires the integrated response of a network of lymphocytes. Both gamma interferon (IFN-γ)- and interleukin 17 (IL-17)-secreting CD4+T cells have been identified in subjects with latent TB infection and during experimentalMycobacterium tuberculosisinfection, but the contribution of Th17 cells to protective immunity is unclear. To examine their protective effectsin vivo, we transferred mycobacterium-specific IL-17- and IFN-γ-secreting CD4+T cells isolated fromM. tuberculosisBCG-immunized IL-12p40−/−and IFN-γ−/−or wild-type mice, respectively, intoM. tuberculosis-infected IL-12p40−/−or RAG−/−mice. In the absence of IL-12 and IL-23, neither IL-17-secreting (Th17) nor IFN-γ-secreting (Th1) BCG-specific T cells expanded or provided protection againstM. tuberculosis. In RAG−/−recipients with an intact IL-12/IL-23 axis, both Th17 and Th1 cells were activated and induced significant protection againstM. tuberculosis. The reduction in the bacterial load following transfer of IFN-γ−/−Th17 cells was associated with significant prolongation of survival compared to recipients of naïve IFN-γ−/−T cells. This effect was at the cost of an increased inflammatory infiltrate characterized by an excess of neutrophils. Therefore, Th17 cells can provide IFN-γ-independent protection againstM. tuberculosis, and this effect may contribute to the early control ofM. tuberculosisinfection.

Từ khóa


Tài liệu tham khảo

10.1038/nature04753

10.1128/IAI.66.5.2122-2127.1998

10.1084/jem.20081463

10.4049/jimmunol.168.3.1322

10.4049/jimmunol.177.3.1416

10.4049/jimmunol.177.10.7086

10.1146/annurev.genom.8.080706.092315

10.4049/jimmunol.172.5.2827

10.1038/ni1254

Jovanovic, D. V., J. A. Di Battista, J. Martel-Pelletier, F. C. Jolicoeur, Y. He, M. Zhang, F. Mineau, and J. P. Pelletier. 1998. IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J. Immunol.160:3513-3521.

10.1038/ni1449

10.4049/jimmunol.175.2.788

10.1084/jem.20061308

10.4049/jimmunol.177.7.4662

10.1038/nature04754

10.1128/IAI.02004-05

10.1146/annurev.immunol.22.012703.104635

10.4049/jimmunol.168.11.5699

10.1038/ni1261

10.1128/IAI.68.2.577-583.2000

10.1038/cmi.2008.25

10.4049/jimmunol.174.8.4852

10.4049/jimmunol.180.3.1962

10.4049/jimmunol.178.6.3786

10.1016/j.immuni.2006.01.001

10.4049/jimmunol.177.12.8684

10.1128/IAI.74.1.557-565.2006

10.1084/jem.194.4.519

10.1016/j.cell.2006.02.013

Thông tin
Thông tin xuất bản

Infection and Immunity

Tập 78 Số 10

4187-4194

Thông tin tác giả