title: Divergent Annexin A1 expression in periphery and gut is associated with systemic immune activation and impaired gut immune response during SIV infection.
abstract: HIV-1 disease progression is paradoxically characterized by systemic chronic immune activation and gut mucosal immune dysfunction, which is not fully defined. Annexin A1 (ANXA1), an inflammation modulator, is a potential link between systemic inflammation and gut immune dysfunction during the simian immunodeficiency virus (SIV) infection. Gene expression of ANXA1 and cytokines were assessed in therapy-naïve rhesus macaques during early and chronic stages of SIV infection and compared with SIV-negative controls. ANXA1 expression was suppressed in the gut but systemically increased during early infection. Conversely, ANXA1 expression increased in both compartments during chronic infection. ANXA1 expression in peripheral blood was positively correlated with HLA-DR+CD4+ and CD8+ T-cell frequencies, and negatively associated with the expression of pro-inflammatory cytokines and CCR5. In contrast, the gut mucosa presented an anergic cytokine profile in relation to ANXA1 expression. In vitro stimulations with ANXA1 peptide resulted in decreased inflammatory response in PBMC but increased activation of gut lymphocytes. Our findings suggest that ANXA1 signaling is dysfunctional in SIV infection, and may contribute to chronic inflammation in periphery and with immune dysfunction in the gut mucosa. Thus, ANXA1 signaling may be a novel therapeutic target for the resolution of immune dysfunction in HIV infection.
authors.affiliation: Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, MG, Brazil.|Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.
authors.forename: Angela A S
authors.initials: AA
authors.lastname: Sena
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Glavan
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.
authors.forename: Guochun
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.
authors.forename: Sumathi
authors.initials: S
authors.lastname: Sankaran-Walters
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Grishina
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.
authors.forename: Satya
authors.initials: S
authors.lastname: Dandekar
authors.affiliation: Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, MG, Brazil.|Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Goulart
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis; D041981:Gastrointestinal Tract / Q000473:pathology*; D020869:Gene Expression Profiling; D018928:Immunity, Mucosal; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology*; D015302:Simian Immunodeficiency Virus / Q000254:growth & development / Q000276:immunology*
chemical_list: D017305:Annexin A1; D016207:Cytokines