The mannose cap of mycobacterial lipoarabinomannan does not dominate the Mycobacterium-host interaction

被引：87

作者：

Appelmelk, B. J. ^{[1
]}

den Dunnen, J. ^{[2
]}

Driessen, N. N. ^{[1
]}

Ummels, R. ^{[1
,3
]}

Pak, M. ^{[4
]}

Nigou, J. ^{[5
]}

Larrouy-Maumus, G. ^{[5
]}

Gurcha, S. S. ^{[6
]}

Movahedzadeh, F. ^{[7
]}

Geurtsen, J. ^{[1
]}

Brown, E. J. ^{[4
]}

Smeets, M. M. Eysink ^{[1
]}

Besra, G. S. ^{[6
]}

Willemsen, P. T. J. ^{[8
]}

Lowary, T. L. ^{[9
,10
]}

van Kooyk, Y. ^{[2
]}

Maaskant, J. J. ^{[1
]}

Stoker, N. G. ^{[7
]}

van der Ley, P. ^{[3
]}

Puzo, G. ^{[5
]}

Vandenbroucke-Grauls, C. M. J. E. ^{[1
]}

Wieland, C. W. ^{[11
]}

van der Poll, T. ^{[11
]}

Geijtenbeek, T. B. H. ^{[2
]}

van der Sar, A. M. ^{[1
]}

Bitter, W. ^{[1
]}

机构：

[1] Vrije Univ Amsterdam, Med Ctr, Dept Med Microbiol & Infect Control, NL-1081 BT Amsterdam, Netherlands

[2] Vrije Univ Amsterdam, Med Ctr, Dept Mol Cell Biol, NL-1081 BT Amsterdam, Netherlands

[3] Netherlands Vaccine Inst, NL-3720 AL Bilthoven, Netherlands

[4] Univ Calif San Francisco, Program Microbial Pathogenesis & Host Def, San Francisco, CA 94143 USA

[5] CNRS, Dept Mecanismes Mol Infect Mycobacteriennes, Inst Pharmacol & Biol Struct, UMR 5089, F-31077 Toulouse 4, France

[6] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England

[7] Univ London Royal Vet Coll, Dept Pathol & Infect Dis, London NW1 0TU, England

[8] CIDC Lelystad, Cent Inst Anim Dis Control, Dept Bacteriol & TSEs, NL-8203 AA Lelystad, Netherlands

[9] Univ Alberta, Dept Chem, Edmonton, AB T6G 2G2, Canada

[10] Univ Alberta, Alberta Ingenu Ctr Carbohydrate Sci, Edmonton, AB T6G 2G2, Canada

[11] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam CINIMA, NL-1105 AZ Amsterdam, Netherlands

来源：

CELLULAR MICROBIOLOGY | 2008年 / 10卷 / 04期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1111/j.1462-5822.2007.01097.x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Pathogenic mycobacteria have the ability to persist in phagocytic cells and to suppress the immune system. The glycolipid lipoarabinomannan (LAM), in particular its mannose cap, has been shown to inhibit phagolysosome fusion and to induce immunosuppressive IL-10 production via interaction with the mannose receptor or DC-SIGN. Hence, the current paradigm is that the mannose cap of LAM is a crucial factor in mycobacterial virulence. However, the above studies were performed with purified LAM, never with live bacteria. Here we evaluate the biological properties of capless mutants of Mycobacterium marinum and M. bovis BCG, made by inactivating homologues of Rv1635c. We show that its gene product is an undecaprenyl phosphomannose-dependent mannosyltransferase. Compared with parent strain, capless M. marinum induced slightly less uptake by and slightly more phagolysosome fusion in infected macrophages but this did not lead to decreased survival of the bacteria in vitro, nor in vivo in zebra fish. Loss of caps in M. bovis BCG resulted in a sometimes decreased binding to human dendritic cells or DC-SIGN-transfected Raji cells, but no differences in IL-10 induction were observed. In mice, capless M. bovis BCG did not survive less well in lung, spleen or liver and induced a similar cytokine profile. Our data contradict the current paradigm and demonstrate that mannose-capped LAM does not dominate the Mycobacterium-host interaction.

引用

页码：930 / 944

页数：15

共 49 条

[1] A specific secretion system mediates PPE41 transport in pathogenic mycobacteria [J].