Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut.
Gut mucosal barrier breakdown and inflammation have been associated with high levels of flagellin, the principal bacterial flagellar protein. Although several gut commensals can produce flagella, flagellin levels are low in the healthy gut, suggesting the existence of control mechanisms. We find that mice lacking the flagellin receptor Toll-like receptor 5 (TLR5) exhibit a profound loss of flagellin-specific immunoglobulins (Igs) despite higher total Ig levels in the gut. Ribotyping of IgA-coated cecal microbiota showed Proteobacteria evading antibody coating in the TLR5(-/-) gut. A diversity of microbiome members overexpressed flagellar genes in the TLR5(-/-) host. Proteobacteria and Firmicutes penetrated small intestinal villi, and flagellated bacteria breached the colonic mucosal barrier. In vitro, flagellin-specific Ig inhibited bacterial motility and downregulated flagellar gene expression. Thus, innate-immunity-directed development of flagellin-specific adaptive immune responses can modulate the microbiome's production of flagella in a three-way interaction that helps to maintain mucosal barrier integrity and homeostasis.
Department of Microbiology, Cornell University, Ithaca, NY 14853, USA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Tyler C
TC
Cullender
Benoit
B
Chassaing
Anders
A
Janzon
Krithika
K
Kumar
Catherine E
CE
Muller
Jeffrey J
JJ
Werner
Largus T
LT
Angenent
M Elizabeth
ME
Bell
Anthony G
AG
Hay
Daniel A
DA
Peterson
Jens
J
Walter
Matam
M
Vijay-Kumar
Andrew T
AT
Gewirtz
Ruth E
RE
Ley
D056704:Adaptive Immunity; D000818:Animals; D005407:Flagella / Q000276:immunology; D005408:Flagellin / Q000276:immunology*; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000382:microbiology*; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology; D008124:Locomotion; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota / Q000276:immunology*; D051198:Toll-Like Receptor 5 / Q000172:deficiency / Q000276:immunology
D007070:Immunoglobulin A; D051198:Toll-Like Receptor 5; D005408:Flagellin