title: The cell surface receptor Slamf6 modulates innate immune responses during Citrobacter rodentium-induced colitis.
abstract: The homophilic cell surface receptors CD150 (Slamf1) and CD352 (Slamf6) are known to modulate adaptive immune responses. Although the Th17 response was enhanced in Slamf6(-/-) C57BL/6 mice upon oral infection with Citrobacter rodentium, the pathologic consequences are indistinguishable from an infection of wild-type C57BL/6 mice. Using a reporter-based binding assay, we show that Slamf6 can engage structures on the outer cell membrane of several Gram(-) bacteria. Therefore, we examined whether Slamf6, like Slamf1, is also involved in innate responses to bacteria and regulates peripheral inflammation by assessing the outcome of C. rodentium infections in Rag(-/-) mice. Surprisingly, the pathology and immune responses in the lamina propria of C. rodentium-infected Slamf6(-/-) Rag(-/-) mice were markedly reduced as compared with those of Rag(-/-) mice. Infiltration of inflammatory phagocytes into the lamina propria was consistently lower in Slamf6(-/-) Rag(-/-) mice than in Rag(-/-) animals. Concomitant with the reduced systemic translocation of the bacteria was an enhanced production of IL-22, suggesting that Slamf6 suppresses a mucosal protective program. Furthermore, administering a mAb (330) that inhibits bacterial interactions with Slamf6 to Rag(-/-) mice ameliorated the infection compared with a control antibody. We conclude that Slamf6-mediated interactions of colonic innate immune cells with specific Gram(-) bacteria reduce mucosal protection and enhance inflammation, contributing to lethal colitis that is caused by C. rodentium infections in Rag(-/-) mice.
authors.affiliation: Department of Medicine, Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02115, MA, USA.
authors.forename: Boaz
authors.initials: B
authors.lastname: van Driel
authors.affiliation: Department of Medicine, Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02115, MA, USA.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Medicine, Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02115, MA, USA.
authors.forename: Gongxian
authors.initials: G
authors.lastname: Liao
authors.affiliation: Department of Medicine, Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02115, MA, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Halibozek
authors.affiliation: Department of Medicine, Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02115, MA, USA.
authors.forename: Marton
authors.initials: M
authors.lastname: Keszei
authors.affiliation: Department of Medicine, Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02115, MA, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: O'Keeffe
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, MA, USA.
authors.forename: Atul K
authors.initials: AK
authors.lastname: Bhan
authors.affiliation: Department of Medicine, Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02115, MA, USA.
authors.forename: Ninghai
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Medicine, Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02115, MA, USA cterhors@bidmc.harvard.edu.
authors.forename: Cox
authors.initials: C
authors.lastname: Terhorst
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D044082:Citrobacter rodentium / Q000276:immunology*; D003092:Colitis / Q000276:immunology* / Q000382:microbiology; D003106:Colon / Q000276:immunology / Q000382:microbiology; D007113:Immunity, Innate / Q000276:immunology*; D007378:Interleukins / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000276:immunology*; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D058504:Th17 Cells / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D015703:Antigens, CD; D007378:Interleukins; D011956:Receptors, Cell Surface; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D000097043:Interleukin-22; C000604062:Slamf1 protein, mouse; C000604063:Slamf6 protein, mouse
keywords: Citrobacter rodentium; IL-22; Slamf6; innate; mucosal immunology