Specificity of the zebrafish host transcriptome response to acute and chronic mycobacterial infection and the role of innate and adaptive immune components

被引:87
作者
van der Sar, Astrid M. [2 ]
Spaink, Herman P. [1 ]
Zakrzewska, Anna [1 ]
Bitter, Wilbert [2 ]
Meijer, Annemarie H. [1 ]
机构
[1] Leiden Univ, Inst Biol, NL-2333 CC Leiden, Netherlands
[2] Vrije Univ Amsterdam, Med Ctr, Dept Med Microbiol & Infect Control, NL-1081 BT Amsterdam, Netherlands
关键词
Tuberculosis; Microarray; TLR; WNT; Matrix metalloproteinases; Small GTPase signaling; MHC class I; GENE-EXPRESSION; PHAGOSOME MATURATION; MATRIX METALLOPROTEINASES; GRANULOMA-FORMATION; IFN-GAMMA; TUBERCULOSIS INFECTION; MARINUM INFECTION; MONONUCLEAR-CELLS; EARLY MACROPHAGES; ADULT ZEBRAFISH;
D O I
10.1016/j.molimm.2009.03.024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pathogenic mycobacteria have the ability to survive within macrophages and persist inside granulomas. The complex host-pathogen interactions that determine the outcome of a mycobacterial infection process result in marked alterations of the host gene expression profile. Here we used the zebrafish model to investigate the specificity of the host response to infections with two mycobacterium strains that give distinct disease outcomes: an acute disease with early lethality or a chronic disease with granuloma formation, caused by Mycobacterium marinum strains Mma20 and E11, respectively. We performed a microarray study of different stages of disease progression in adult zebrafish and found that the acute and the chronic strains evoked partially overlapping host transcriptome signatures, despite that they induce profoundly different disease phenotypes. Both strains affected many signaling cascades, including WNT and TLR pathways. Interestingly, the strongest differences were observed at the initial stage of the disease. The immediate response to the acute strain was characterized by higher expression of genes encoding MHC class I proteins, matrix metalloproteinases, transcription factors, cytokines and other common immune response proteins. In contrast, small GTPase and histone gene groups showed higher expression in response to the chronic strain. We also found that nearly 1000 mycobacterium-responsive genes overlapped between the expression signatures of infected zebrafish adults and embryos at different stages of granuloma formation. Since adult zebrafish possess an adaptive immune system similar to mammals and zebrafish embryos rely solely on innate immunity, this overlap indicates a major contribution of the innate component of the immune system in the response to mycobacterial infection. Taken together, our comparison of the transcriptome responses involved in acute versus chronic infections and in the embryonic versus adult situation provides important new leads for investigating the mechanism of mycobacterial pathogenesis. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2317 / 2332
页数:16
相关论文
共 94 条
[91]  
2-3
[92]   ADAM, A NOVEL FAMILY OF MEMBRANE-PROTEINS CONTAINING A DISINTEGRIN AND METALLOPROTEASE DOMAIN - MULTIPOTENTIAL FUNCTIONS IN CELL-CELL AND CELL-MATRIX INTERACTIONS [J].
WOLFSBERG, TG ;
PRIMAKOFF, P ;
MYLES, DG ;
WHITE, JM .
JOURNAL OF CELL BIOLOGY, 1995, 131 (02) :275-278
[93]   ADAM family proteins in the immune system [J].
Yamamoto, S ;
Higuchi, Y ;
Yoshiyama, K ;
Shimizu, E ;
Kataoka, M ;
Hijiya, N ;
Matsuura, K .
IMMUNOLOGY TODAY, 1999, 20 (06) :278-284
[94]   Coordinated down-regulation of the antigen processing machinery in the gills of amoebic gill disease-affected Atlantic salmon (Salmo salar L.) [J].
Young, N. D. ;
Cooper, G. A. ;
Nowak, B. F. ;
Koop, B. F. ;
Morrison, R. N. .
MOLECULAR IMMUNOLOGY, 2008, 45 (09) :2581-2597