title: Mice lacking SIGNR1 have stronger T helper 1 responses to Mycobacterium tuberculosis.
abstract: Mycobacterium tuberculosis and the associated disease tuberculosis are health risks causing many deaths worldwide each year in humans. M. tuberculosis targets dendritic cell (DC)-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) to induce immunosuppression, since interaction of DC-SIGN with mycobacterial mannose-capped lipoarabinomannan (ManLAM) induces interleukin (IL)-10 and prevents DC maturation. We investigated the role of a murine homolog of DC-SIGN, SIGN Related 1 (SIGNR1), in a model of M. tuberculosis infection using SIGNR1 deficient (KO) mice. Although SIGNR1 is expressed by macrophages and not by DCs, it also interacts with M. tuberculosis similar to DC-SIGN. Peritoneal macrophages from SIGNR1 KO mice produce less IL-10 upon stimulation with ManLAM than those from wild-type mice, suggesting that the interaction of ManLAM with SIGNR1 can result in immunosuppression similar to its human homolog. Indeed, early in infection, we observed increased T cell activity in SIGNR1 KO mice and increased IFNgamma production by splenocytes in SIGNR1 KO mice. However, we did not detect any differences between WT and KO mice in mycobacterial loads in the lungs or distant organs after M. tuberculosis infection resulting in similar survival rates. Moreover, we found that SIGNR1 is not present on alveolar macrophages of uninfected mice nor is it induced on lung macrophages throughout infection. Therefore, our data suggest that although SIGNR1 has a similar binding specificity as DC-SIGN, its role is limited during murine M. tuberculosis infection.
authors.affiliation: Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Catharina W
authors.initials: CW
authors.lastname: Wieland
authors.forename: Estella A
authors.initials: EA
authors.lastname: Koppel
authors.forename: Jeroen
authors.initials: J
authors.lastname: den Dunnen
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D006651:Histocytochemistry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008853:Microscopy; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D013534:Survival; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D007371:Interferon-gamma; D016753:Interleukin-10; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C050016:lipoarabinomannan