Research in my laboratory focuses on two main areas: 1) co-factors that influence the mucosal transmission of HIV-1; and 2) the role of endogenous nucleic acid autoantigens as mediators of systemic lupus erythematosus.
1) Mucosal immune responses of the lower female reproductive tract to sexually transmitted pathogenic microorganisms leads to an inflammatory response that enhances the heterosexual transmission of HIV-1. Inflammation is initiated largely by signaling through members of the Toll-like family of innate immune receptors (TLR) that are activated by pathogen-encoded ligands. This inflammatory response enhances HIV-1 transmission by inducing the recruitment of target immune cells such as Langerhans/dendritic cells (LC/DC), macrophages (MØ)‚ and T lymphocytes to the mucosa and by direct activation of these cells. Recent findings have demonstrated that activation of certain nuclear receptors (NR), including peroxisome proliferator activated receptor (PPAR), liver X receptor (LXR), and glucocorticoid receptor (GR)) potently inhibits TLR-induced inflammatory gene expression in MØ, LC/DC, and epithelial cells. Studies in our laboratory are directed toward evaluating: 1) the ability of ligand-activated NR to inhibit the mucosal transmission of HIV-1, in particular LC/DC-mediated trans-infection of T cells; and 2) the molecular mechanism(s) of how ligand-activated NR inhibit TLR-induced transcription of both HIV-1 and inflammatory cytokine genes.
2) Autoimmune diseases such as systemic lupus erythematosus (SLE) are characterized by the overproduction of antibodies, many of which recognize ribonucleoprotein and/or chromatin related autoantigens. A common feature of these autoantigens is that they include DNA or RNA. Our laboratory, in collaboration with Dr. Ann Marshak-Rothstein, is defining the protein and nucleic acid composition of these immunostimulatory autoantigens and determining whether different forms of apoptosis are capable of selectively releasing these autoantigens from cells, thereby making them accessible to autoreactive B cells.
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
- University of Minnesota, PhD
- Lafayette College, BA
- Published on 9/16/2016
Agosto LM, Hirnet JB, Michaels DH, Shaik-Dasthagirisaheb YB, Gibson FC, Viglianti G, Henderson AJ. Porphyromonas gingivalis-mediated signaling through TLR4 mediates persistent HIV infection of primary macrophages. Virology. 2016 Dec; 499:72-81. PMID: 27639573.
- Published on 8/26/2016
Papadopoulos G, Shaik-Dasthagirisaheb YB, Huang N, Viglianti GA, Henderson AJ, Kantarci A, Gibson FC. Immunologic environment influences macrophage response to Porphyromonas gingivalis. Mol Oral Microbiol. 2017 Jun; 32(3):250-261. PMID: 27346827.
- Published on 1/1/2016
Moody KL, Uccellini MB, Avalos AM, Marshak-Rothstein A, Viglianti GA. Toll-Like Receptor-Dependent Immune Complex Activation of B Cells and Dendritic Cells. Methods Mol Biol. 2016; 1390:249-72. PMID: 26803634.
- Published on 2/20/2015
Kaczmarek Michaels K, Natarajan M, Euler Z, Alter G, Viglianti G, Henderson AJ. Blimp-1, an intrinsic factor that represses HIV-1 proviral transcription in memory CD4+ T cells. J Immunol. 2015 Apr 1; 194(7):3267-74. PMID: 25710909.
- Published on 1/21/2012
Uccellini MB, Busto P, Debatis M, Marshak-Rothstein A, Viglianti GA. Selective binding of anti-DNA antibodies to native dsDNA fragments of differing sequence. Immunol Lett. 2012 Mar 30; 143(1):85-91. PMID: 22285306.
- Published on 8/17/2011
Hanley TM, Viglianti GA. Nuclear receptor signaling inhibits HIV-1 replication in macrophages through multiple trans-repression mechanisms. J Virol. 2011 Oct; 85(20):10834-50. PMID: 21849441.
- Published on 10/1/2010
Avalos AM, Uccellini MB, Lenert P, Viglianti GA, Marshak-Rothstein A. Fc?RIIB regulation of BCR/TLR-dependent autoreactive B-cell responses. Eur J Immunol. 2010 Oct; 40(10):2692-8. PMID: 20809520.
- Published on 7/1/2010
Hanley TM, Blay Puryear W, Gummuluru S, Viglianti GA. PPARgamma and LXR signaling inhibit dendritic cell-mediated HIV-1 capture and trans-infection. PLoS Pathog. 2010; 6:e1000981. PMID: 20617179.
- Published on 7/31/2009
Yasuda K, Richez C, Uccellini MB, Richards RJ, Bonegio RG, Akira S, Monestier M, Corley RB, Viglianti GA, Marshak-Rothstein A, Rifkin IR. Requirement for DNA CpG content in TLR9-dependent dendritic cell activation induced by DNA-containing immune complexes. J Immunol. 2009 Sep 1; 183(5):3109-17. PMID: 19648272.
- Published on 1/1/2009
Uccellini MB, Avalos AM, Marshak-Rothstein A, Viglianti GA. Toll-like receptor-dependent immune complex activation of B cells and dendritic cells. Methods Mol Biol. 2009; 517:363-80. PMID: 19378022.
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