title: Segmented filamentous bacterium uses secondary and tertiary lymphoid tissues to induce gut IgA and specific T helper 17 cell responses.
abstract: Segmented filamentous bacterium (SFB) is a symbiont that drives postnatal maturation of gut adaptive immune responses. In contrast to nonpathogenic E. coli, SFB stimulated vigorous development of Peyer's patches germinal centers but paradoxically induced only a low frequency of specific immunoglobulin A (IgA)-secreting cells with delayed accumulation of somatic mutations. Moreover, blocking Peyer's patch development abolished IgA responses to E. coli, but not to SFB. Indeed, SFB stimulated the postnatal development of isolated lymphoid follicles and tertiary lymphoid tissue, which substituted for Peyer's patches as inductive sites for intestinal IgA and SFB-specific T helper 17 (Th17) cell responses. Strikingly, in mice depleted of gut organized lymphoid tissue, SFB still induced a substantial but nonspecific intestinal Th17 cell response. These results demonstrate that SFB has the remarkable capacity to induce and stimulate multiple types of intestinal lymphoid tissues that cooperate to generate potent IgA and Th17 cell responses displaying only limited target specificity.
authors.affiliation: INSERM UMR1163, Laboratory of Intestinal Immunity; Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, 75015 Paris, France.
authors.forename: Emelyne
authors.initials: E
authors.lastname: Lécuyer
authors.affiliation: INSERM UMR1163, Laboratory of Intestinal Immunity; Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, 75015 Paris, France; INRA Micalis UMR1319, 78350 Jouy-en-Josas, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Rakotobe
authors.affiliation: INSERM UMR1163, Laboratory of Intestinal Immunity; Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, 75015 Paris, France; AP-HP, Department of Pediatric Gastroenterology, Hôpital Necker, 75015 Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Lengliné-Garnier
authors.affiliation: INSERM UMR1163, Laboratory of Intestinal Immunity; Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, 75015 Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Lebreton
authors.affiliation: INSERM UMR1163, Laboratory of Intestinal Immunity; Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, 75015 Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Picard
authors.affiliation: INRA Micalis UMR1319, 78350 Jouy-en-Josas, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Juste
authors.affiliation: Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, 75015 Paris, France; INSERM UMR 1151, Institut Necker-Enfants Malades, Université Paris Descartes- Sorbonne Paris Cité, 75014 Paris, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Fritzen
authors.affiliation: Institut Pasteur, Lymphoid Tissue Development Unit, 75015 Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Eberl
authors.affiliation: Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3008 Bern, Switzerland.
authors.forename: Kathy D
authors.initials: KD
authors.lastname: McCoy
authors.affiliation: Maurice Müller Laboratories, Universitätsklinik für Viszerale Chirurgie und Medizin (UVCM), University of Bern, 3008 Bern, Switzerland.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Macpherson
authors.affiliation: Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, 75015 Paris, France; INSERM UMR 1151, Institut Necker-Enfants Malades, Université Paris Descartes- Sorbonne Paris Cité, 75014 Paris, France.
authors.forename: Claude-Agnès
authors.initials: CA
authors.lastname: Reynaud
authors.affiliation: INSERM UMR1163, Laboratory of Intestinal Immunity; Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, 75015 Paris, France. Electronic address: nadine.cerf-bensussan@inserm.fr.
authors.forename: Nadine
authors.initials: N
authors.lastname: Cerf-Bensussan
authors.affiliation: INSERM UMR1163, Laboratory of Intestinal Immunity; Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, 75015 Paris, France; INRA Micalis UMR1319, 78350 Jouy-en-Josas, France. Electronic address: valerie.gaboriau-routhiau@inserm.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gaboriau-Routhiau
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002450:Cell Communication; D002454:Cell Differentiation; D003013:Clostridium / Q000276:immunology*; D003015:Clostridium Infections / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology*; D054884:Host-Pathogen Interactions; D007070:Immunoglobulin A / Q000378:metabolism*; D007422:Intestines / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D007070:Immunoglobulin A