title: Absence of Annexin A1 impairs host adaptive immunity against Mycobacterium tuberculosis in vivo.
abstract: The role of Annexin A1 (ANXA1) in counter-regulating the activities of innate immune cells, such as the migration of neutrophils and monocytes, and the generation of pro-inflammatory mediators in various models of inflammatory and autoimmune diseases is well documented. However, while ANXA1 has been proposed as an important mediator of the adaptive immune response, its involvement in this respect has been less studied. Furthermore, while there have been numerous studies on the role of ANXA1 in inflammatory diseases, less has been reported on its influence in immunity against infection. A recent study reported a link between ANXA1 and tuberculosis, and proposed a model in which Mycobacterium tuberculosis exerts its virulence by manipulating the ANXA1-mediated host apoptotic response. This has prompted us to further investigate the role of ANXA1 in the pathogenesis of tuberculosis in vivo. Here, we show that ANXA1(-/-) mice are more susceptible to M. tuberculosis infection, as evidenced by a transient increase in the pulmonary bacterial burden, and exacerbated and disorganized granulomatous inflammation. These pathological manifestations correlated with an impaired ability of ANXA1(-/-) dendritic cells to activate naïve T cells, thereby supporting a role for ANXA1 in shaping the adaptive immunity against M. tuberculosis.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore; Immunology Programme, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Koh Hui Qi
authors.initials: KH
authors.lastname: Vanessa
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore; Immunology Programme, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Martínez Gómez
authors.initials: MG
authors.lastname: Julia
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore; Immunology Programme, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Lin
authors.initials: L
authors.lastname: Wenwei
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore; Immunology Programme, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Ang Lay Teng
authors.initials: AL
authors.lastname: Michelle
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore; Immunology Programme, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Zainul Rahim Siti
authors.initials: ZR
authors.lastname: Zarina
authors.affiliation: Immunology Programme, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: lina_lim@nuhs.edu.sg.
authors.forename: Lim Hsiu Kim
authors.initials: LH
authors.lastname: Lina
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore; Immunology Programme, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore. Electronic address: micas@nus.edu.sg.
authors.forename: Alonso
authors.initials: A
authors.lastname: Sylvie
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D006099:Granuloma / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
chemical_list: D017305:Annexin A1
keywords: Adaptive immunity; Annexin A1; Granuloma; Tuberculosis