title: Down-regulation of complement receptors on the surface of host monocyte even as in vitro complement pathway blocking interferes in dengue infection.
abstract: In dengue virus (DENV) infection, complement system (CS) activation appears to have protective and pathogenic effects. In severe dengue fever (DF), the levels of DENV non-structural-1 protein and of the products of complement activation, including C3a, C5a and SC5b-9, are higher before vascular leakage occurs, supporting the hypothesis that complement activation contributes to unfavourable outcomes. The clinical manifestations of DF range from asymptomatic to severe and even fatal. Here, we aimed to characterise CS by their receptors or activation product, in vivo in DF patients and in vitro by DENV-2 stimulation on monocytes. In comparison with healthy controls, DF patients showed lower expression of CR3 (CD11b), CR4 (CD11c) and, CD59 on monocytes. The DF patients who were high producers of SC5b-9 were also those that showed more pronounced bleeding or vascular leakage. Those findings encouraged us to investigate the role of CS in vitro, using monocytes isolated from healthy subjects. Prior blocking with CR3 alone (CD11b) or CR3 (CD11b/CD18) reduced viral infection, as quantified by the levels of intracellular viral antigen expression and soluble DENV non-structural viral protein. However, we found that CR3 alone (CD11b) or CR3 (CD11b/CD18) blocking did not influence major histocompatibility complex presentation neither active caspase-1 on monocytes, thus probably ruling out inflammasome-related mechanisms. Although it did impair the secretion of tumour necrosis factor alpha and interferon alpha. Our data provide strategies of blocking CR3 (CD11b) pathways could have implications for the treatment of viral infection by antiviral-related mechanisms.
authors: Laboratory of Viral Immunology, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
authors: Cintia Ferreira
authors: CF
authors: Marinho
authors: Laboratory of Viral Immunology, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
authors: Elzinandes Leal
authors: EL
authors: Azeredo
authors: Laboratory of Viral Immunology, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
authors: Amanda
authors: A
authors: Torrentes-Carvalho
authors: Flow Cytometry Sector, Centre for Cell Sorting and Analysis, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
authors: Alessandro
authors: A
authors: Marins-Dos-Santos
authors: Laboratory of Viral Immunology, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
authors: Claire Fernandes
authors: CF
authors: Kubelka
authors: Referral Centre for Dengue, Campos de Goytacazes, Brazil.
authors: Luiz José
authors: LJ
authors: de Souza
authors: Department of Clinical Medicine, Universidade Federal do Mato Grosso do Sul, Campo Grande, Brazil.
authors: Rivaldo Venâncio
authors: RV
authors: Cunha
authors: Laboratory of Viral Immunology, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
authors: Luzia Maria
authors: LM
authors: de-Oliveira-Pinto
mesh_terms: D000328:Adult; D020170:Caspase 1 / Q000276:immunology; D003167:Complement Activation / Q000276:immunology; D015926:Complement C3a / Q000096:biosynthesis / Q000276:immunology; D015936:Complement C5a / Q000096:biosynthesis / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000096:biosynthesis / Q000276:immunology; D003716:Dengue Virus / Q000276:immunology* / Q000472:pathogenicity; D005260:Female; D015967:Gene Expression Regulation, Viral; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000235:genetics / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D019595:Severe Dengue / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000276:immunology
chemical_list: D015938:Complement Membrane Attack Complex; D016167:Integrin alphaXbeta2; D016177:Macrophage-1 Antigen; C047610:SC5b-9 protein complex; D017361:Viral Nonstructural Proteins; D015926:Complement C3a; D015936:Complement C5a; D020170:Caspase 1