Reversible Microbial Colonization of Germ-Free Mice Reveals the Dynamics of IgA Immune Responses

被引:591
作者
Hapfelmeier, Siegfried [1 ,2 ]
Lawson, Melissa A. E. [2 ]
Slack, Emma [1 ,2 ]
Kirundi, Jorum K. [1 ,2 ]
Stoel, Maaike [2 ]
Heikenwalder, Mathias [3 ]
Cahenzli, Julia [2 ]
Velykoredko, Yuliya [2 ]
Balmer, Maria L. [1 ]
Endt, Kathrin [4 ]
Geuking, Markus B. [2 ]
Curtiss, Roy, III [5 ]
McCoy, Kathy D. [2 ]
Macpherson, Andrew J. [1 ,2 ]
机构
[1] Univ Bern, Univ Klin Viszerale Chirurg & Med UVCM, DKF Maurice Muller Labs, MEM, CH-3013 Bern, Switzerland
[2] McMaster Univ, Farncombe Family Digest Hlth Res Inst, Hamilton, ON L8N 3Z5, Canada
[3] Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland
[4] Fed Inst Technol, Inst Microbiol, CH-8093 Zurich, Switzerland
[5] Arizona State Univ, Biodesign Inst, Ctr Infect Dis & Vaccinol, Tempe, AZ 85287 USA
基金
瑞士国家科学基金会; 加拿大健康研究院;
关键词
PLASMA-CELLS; COMMENSAL BACTERIA; T-CELLS; MEMORY; MAINTENANCE; GUT;
D O I
10.1126/science.1188454
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The lower intestine of adult mammals is densely colonized with nonpathogenic (commensal) microbes. Gut bacteria induce protective immune responses, which ensure host-microbial mutualism. The continuous presence of commensal intestinal bacteria has made it difficult to study mucosal immune dynamics. Here, we report a reversible germ-free colonization system in mice that is independent of diet or antibiotic manipulation. A slow (more than 14 days) onset of a long-lived (half-life over 16 weeks), highly specific anticommensal immunoglobulin A (IgA) response in germ-free mice was observed. Ongoing commensal exposure in colonized mice rapidly abrogated this response. Sequential doses lacked a classical prime-boost effect seen in systemic vaccination, but specific IgA induction occurred as a stepwise response to current bacterial exposure, such that the antibody repertoire matched the existing commensal content.
引用
收藏
页码:1705 / 1709
页数:5
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