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: Catharina W Wieland, Estella A Koppel, Jeroen den Dunnen, Sandrine Florquin, Andrew N J McKenzie, Yvette van Kooyk, Tom van der Poll, Teunis B H Geijtenbeek
• Journal: Microbes and infection (Microbes Infect) Vol. 9 Issue 2 Pg. 134-41 (Feb 2007) ISSN: 1286-4579 [Print] France
• PMID: 17224292 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules
• DC-specific ICAM-3 grabbing nonintegrin
• Lectins, C-Type
• Lipopolysaccharides
• Receptors, Cell Surface
• lipoarabinomannan
• Interleukin-10
• Interferon-gamma

Topics

• Animals
• Cell Adhesion Molecules (deficiency, genetics, physiology)
• Colony Count, Microbial
• Disease Models, Animal
• Histocytochemistry
• Humans
• Interferon-gamma (biosynthesis)
• Interleukin-10 (biosynthesis)
• Lectins, C-Type (deficiency, genetics, physiology)
• Lipopolysaccharides (immunology, metabolism)
• Liver (microbiology)
• Lung (microbiology, pathology)
• Macrophages (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microscopy
• Mycobacterium tuberculosis (immunology)
• Receptors, Cell Surface (deficiency, genetics, physiology)
• Spleen (immunology, microbiology)
• Survival
• T-Lymphocytes (immunology)
• Tuberculosis (immunology)