Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism.
Commensal bacteria in the lower intestine of mammals are 10 times as numerous as the body's cells. We investigated the relative importance of different immune mechanisms in limiting the spread of the intestinal microbiota. Here, we reveal a flexible continuum between innate and adaptive immune function in containing commensal microbes. Mice deficient in critical innate immune functions such as Toll-like receptor signaling or oxidative burst production spontaneously produce high-titer serum antibodies against their commensal microbiota. These antibody responses are functionally essential to maintain host-commensal mutualism in vivo in the face of innate immune deficiency. Spontaneous hyper-activation of adaptive immunity against the intestinal microbiota, secondary to innate immune deficiency, may clarify the underlying mechanisms of inflammatory diseases where immune dysfunction is implicated.
Slack
Emma
E
Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada. andrew.macpherson@insel.ch
Hapfelmeier
Siegfried
S
Stecher
Bärbel
B
Velykoredko
Yuliya
Y
Stoel
Maaike
M
Lawson
Melissa A E
MA
Geuking
Markus B
MB
Beutler
Bruce
B
Tedder
Thomas F
TF
Hardt
Wolf-Dietrich
WD
Bercik
Premysl
P
Verdu
Elena F
EF
McCoy
Kathy D
KD
Macpherson
Andrew J
AJ
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D016470:Bacteremia / Q000276:immunology / Q000382:microbiology; D001419:Bacteria / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D001424:Bacterial Infections / Q000276:immunology / Q000382:microbiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015169:Colony Count, Microbial; D013293:Enterococcus faecalis / Q000254:growth & development / Q000276:immunology / Q000302:isolation & purification; D048168:Escherichia coli K12 / Q000254:growth & development / Q000276:immunology / Q000302:isolation & purification; D005856:Germ-Free Life; D007109:Immunity; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology*; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D008221:Lymphoid Tissue / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability; D016897:Respiratory Burst; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000382:microbiology; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
D000907:Antibodies, Bacterial; D051193:Toll-Like Receptors