title: The Tim3-galectin 9 pathway induces antibacterial activity in human macrophages infected with Mycobacterium tuberculosis.
abstract: T cell Ig and mucin domain 3 (Tim3) is an inhibitory molecule involved in immune tolerance, autoimmune responses, and antiviral immune evasion. However, we recently demonstrated that Tim3 and Galectin-9 (Gal9) interaction induces a program of macrophage activation that results in killing of Mycobacterium tuberculosis in the mouse model of infection. In this study, we sought to determine whether the Tim3-Gal9 pathway plays a similar role in human pulmonary TB. We identified that pulmonary TB patients have reduced expression of Tim3 on CD14(+) monocytes in vivo. By blocking Tim3 and Gal9 interaction in vitro, we show that these molecules contribute to the control of intracellular bacterial replication in human macrophages. The antimicrobial effect was partially dependent on the production of IL-1β. Our results establish that Tim3-Gal9 interaction activates human M. tuberculosis -infected macrophages and leads to the control of bacterial growth through the production of the proinflammatory cytokine IL-1β. Data presented in this study suggest that one of the potential pathways activated by Tim3/Gal9 is the secretion of IL-1β, which plays a crucial role in antimicrobial immunity by modulating innate inflammatory networks.
authors.affiliation: Laboratory of Integrative Immunology, National Institute of Respiratory Diseases, Mexico City 14080, Mexico. isadamx@gmail.com
authors.forename: Isabel
authors.initials: I
authors.lastname: Sada-Ovalle
authors.forename: Leslie
authors.initials: L
authors.lastname: Chávez-Galán
authors.forename: Luis
authors.initials: L
authors.lastname: Torre-Bouscoulet
authors.forename: Lourdes
authors.initials: L
authors.lastname: Nava-Gamiño
authors.forename: Lourdes
authors.initials: L
authors.lastname: Barrera
authors.forename: Pushpa
authors.initials: P
authors.lastname: Jayaraman
authors.forename: Martha
authors.initials: M
authors.lastname: Torres-Rojas
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Salazar-Lezama
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Behar
mesh_terms: D000328:Adult; D000368:Aged; D019138:Antibodies, Blocking / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D037161:Galectins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D025941:Protein Interaction Mapping; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human; D008565:Membrane Proteins