title: Linking genetic variation in human Toll-like receptor 5 genes to the gut microbiome's potential to cause inflammation.
abstract: Immunodeficiencies can lead to alterations of the gut microbiome that render it pathogenic and capable of transmitting disease to naïve hosts. Here, we review the role of Toll-like receptor (TLR) 5, the innate receptor for bacterial flagellin, in immune responses to the normal gut microbiota with a focus its role on adaptive immunity. Loss of TLR5 has profound effects on the microbiota that include greater temporal instability of major lineages and upregulation of flagellar motility genes that may be linked to the reduced levels of anti-flagellin antibodies in the TLR5(-/-) host. A variety of human TLR5 gene alleles exist that also associated with inflammatory conditions and may do so via effects on the gut microbiome and altered host-microbial crosstalk.
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, United States. Electronic address: cal59@cornell.edu.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Leifer
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States.
authors.forename: Cameron
authors.initials: C
authors.lastname: McConkey
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States.
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.affiliation: Center for Inflammation, Immunity and Infection, Georgia State University, Atlanta, GA 30303, United States.
authors.forename: Benoit
authors.initials: B
authors.lastname: Chassaing
authors.affiliation: Center for Inflammation, Immunity and Infection, Georgia State University, Atlanta, GA 30303, United States.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Gewirtz
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, United States. Electronic address: rel222@cornell.edu.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Ley
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D005408:Flagellin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051198:Toll-Like Receptor 5; D005408:Flagellin
keywords: Adaptive immunity; Allelic variation; Gut microbiome; Metagenomics; TLR5; Toll-like receptor 5