title: Toll-like receptor expression and function in type I bipolar disorder.
abstract: Bipolar disorder (BD) has been associated with immune imbalance and low-grade inflammation. The underlying mechanisms remain largely obscure but may involve changes in cell signaling. Toll-like receptors (TLRs) are widely expressed by immune cells. Specific binding of TLRs to pathogen- or danger-associated signals leads to inflammatory responses. Here, we analyzed the frequencies of TLR-1, TLR-2, TLR-4, TLR-5 and TLR-6 in monocytes, regulatory T cells (Tregs) and activated T cells from type I BD euthymic patients and healthy controls (HCs). Monocytes were stimulated in vitro with specific TLR agonists (flagellin, LPS, LTA, BLP and PGN) and immunophenotyped. Cytokines (IL-8, IL-1beta, IL-6, IL-10, TNF-alpha and IL-12p70) were assessed with cytometric bead arrays. At baseline, increased percentages of TLR-1+ and TLR-2+ monocytes and reduced expression of TLR-5 were observed in BD. Following stimulation, the percentage of TLR-1+, TLR-2+, and TLR-6+ monocytes was higher in BD subjects than in HCs. Increased levels of IL-8, IL-12p70 and TNF were observed following stimulation with TLR-1, TLR-2 and TLR-6 agonists, suggesting increased signaling via these receptors in BD. In contrast to HCs, BD patients exhibited no changes in TLR-5 expression following stimulation. The percentage of TLR-2+ Treg cells as well as activated T cells expressing both TLR-2 and TLR-5 increased in BD patients. Given the importance of TLRs in triggering immune responses, our data indicate a role for these receptors in the low-grade inflammatory profile documented in BD.
authors.affiliation: Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Postgraduate Program in Biomedical Gerontology, Brazil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wieck
authors.affiliation: Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Cognitive Neuroscience Research Group (GNCD), Centre of Studies and Research in Traumatic Stress (NEPTE), Postgraduate Program in Psychology, PUCRS, Porto Alegre, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Grassi-Oliveira
authors.affiliation: Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
authors.forename: Carine Hartmann
authors.initials: CH
authors.lastname: do Prado
authors.affiliation: Cognitive Neuroscience Research Group (GNCD), Centre of Studies and Research in Traumatic Stress (NEPTE), Postgraduate Program in Psychology, PUCRS, Porto Alegre, Brazil.
authors.forename: Thiago Wendt
authors.initials: TW
authors.lastname: Viola
authors.affiliation: Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
authors.forename: Laura Esteves
authors.initials: LE
authors.lastname: Petersen
authors.affiliation: Lab. Imunologia Clínica e Experimental, Institute of Biomedical Research, Pontifical Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Porto
authors.affiliation: Translational Psychoneuroimmunology Group, School of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil.
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
authors.affiliation: Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Postgraduate Program in Biomedical Gerontology, Brazil. Electronic address: mebauer@pucrs.br.
authors.forename: Moisés Evandro
authors.initials: ME
authors.lastname: Bauer
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping / Q000379:methods; D007249:Inflammation; D007378:Interleukins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D007378:Interleukins; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha
keywords: Bipolar disorder; Inflammation; Innate immunity; Monocytes; Regulatory T cells; Toll-like receptors