Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses.
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.
Hapfelmeier
Siegfried
S
DKF (Maurice Müller Laboratories), MEM, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3013 Bern, Switzerland. hapfelmeier@gmail.com
Lawson
Melissa A E
MA
Slack
Emma
E
Kirundi
Jorum K
JK
Stoel
Maaike
M
Heikenwalder
Mathias
M
Cahenzli
Julia
J
Velykoredko
Yuliya
Y
Balmer
Maria L
ML
Endt
Kathrin
K
Geuking
Markus B
MB
Curtiss
Roy
R
McCoy
Kathy D
KD
Macpherson
Andrew J
AJ
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
D000907:Antibodies, Bacterial; D007070:Immunoglobulin A