Differential activation profiles of Crimean-Congo hemorrhagic fever virus- and Dugbe virus-infected antigen-presenting cells.
Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic, tick-borne member of the family Bunyaviridae and the genus Nairovirus. To better elucidate the pathogenesis of CCHFV, we analysed the host innate immune response induced in antigen-presenting cells (APCs) infected in vitro by CCHFV. Monocyte-derived dendritic cells (DCs) and macrophages (MPs) were both shown to be permissive for CCHFV and to replicate the virus, as monitored by genomic and antigenomic strand quantification. Virus replication was, however, controlled, corroborating an efficient alpha interferon-induced response. The upregulation of CD-83 and CD-86 indicated that CCHFV induced a partial maturation of DCs, which were also shown to activate the secretion of interleukin (IL)-6 and IL-8, but no tumour necrosis factor alpha (TNF-alpha). On the other hand, in MPs, CCHFV infection elicited a high IL-6 and TNF-alpha response and a moderate chemokine response. Nevertheless, when we compared these APC responses with those seen after infection with Dugbe virus (DUGV), a mildly pathogenic virus genetically close to CCHFV, we found that, in spite of some similarities, DUGV induced a higher cytokine/chemokine response in MPs. These results suggest that CCHFV is able to inhibit the activation of inflammatory mediators selectively in infection in vitro and that these differences could be relevant in pathogenesis.
Peyrefitte
Christophe N
CN
Emerging Pathogens Laboratory, Fondation Mérieux, IFR128 BioSciences Lyon-Gerland, Lyon, France.
Perret
Magali
M
Garcia
Stephan
S
Rodrigues
Raquel
R
Bagnaud
Audrey
A
Lacote
Sandra
S
Crance
Jean-Marc
JM
Vernet
Guy
G
Garin
Daniel
D
Bouloy
Michèle
M
Paranhos-Baccalà
Gláucia
G
D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000821:virology*; D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000821:virology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D016855:Nairovirus / Q000276:immunology* / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D014779:Virus Replication; D000097802:CD83 Antigen
D015703:Antigens, CD; D051940:B7-2 Antigen; D018925:Chemokines; D007136:Immunoglobulins; D015850:Interleukin-6; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C497964:CD86 protein, human