title: Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses.
abstract: 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.
authors.affiliation: DKF (Maurice Müller Laboratories), MEM, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3013 Bern, Switzerland. hapfelmeier@gmail.com
authors.forename: Siegfried
authors.initials: S
authors.lastname: Hapfelmeier
authors.forename: Melissa A E
authors.initials: MA
authors.lastname: Lawson
authors.forename: Emma
authors.initials: E
authors.lastname: Slack
authors.forename: Jorum K
authors.initials: JK
authors.lastname: Kirundi
authors.forename: Maaike
authors.initials: M
authors.lastname: Stoel
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.forename: Julia
authors.initials: J
authors.lastname: Cahenzli
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Velykoredko
authors.forename: Maria L
authors.initials: ML
authors.lastname: Balmer
authors.forename: Kathrin
authors.initials: K
authors.lastname: Endt
authors.forename: Markus B
authors.initials: MB
authors.lastname: Geuking
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
authors.forename: Kathy D
authors.initials: KD
authors.lastname: McCoy
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Macpherson
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D000918:Antibody Specificity; D015169:Colony Count, Microbial; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli / Q000254:growth & development* / Q000276:immunology*; D005856:Germ-Free Life; D006207:Half-Life; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology*; D007156:Immunologic Memory; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology*; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology; D013997:Time Factors
chemical_list: D000907:Antibodies, Bacterial; D007070:Immunoglobulin A