Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression.
Arboviruses cause acute diseases that increasingly affect global health. We used bluetongue virus (BTV) and its natural sheep host to reveal a previously uncharacterized mechanism used by an arbovirus to manipulate host immunity. Our study shows that BTV, similarly to other antigens delivered through the skin, is transported rapidly via the lymph to the peripheral lymph nodes. Here, BTV infects and disrupts follicular dendritic cells, hindering B-cell division in germinal centers, which results in a delayed production of high affinity and virus neutralizing antibodies. Moreover, the humoral immune response to a second antigen is also hampered in BTV-infected animals. Thus, an arbovirus can evade the host antiviral response by inducing an acute immunosuppression. Although transient, this immunosuppression occurs at the critical early stages of infection when a delayed host humoral immune response likely affects virus systemic dissemination and the clinical outcome of disease.
MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, Scotland.
Eleonora
E
Melzi
MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, Scotland; Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise "G. Caporale", 64100 Teramo, Italy.
Marco
M
Caporale
Moredun Research Institute, Penicuik EH26 0PZ, Scotland.
Mara
M
Rocchi
Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos-Madrid 28130, Spain.
Verónica
V
Martín
Division of Pathology, Public Health and Disease Investigation, School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, Scotland.
Virginia
V
Gamino
Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise "G. Caporale", 64100 Teramo, Italy.
Andrea
A
di Provvido
Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise "G. Caporale", 64100 Teramo, Italy; Facoltà di Medicina Veterinaria, Università di Teramo, 64100 Teramo, Italy.
Giuseppe
G
Marruchella
Moredun Research Institute, Penicuik EH26 0PZ, Scotland.
Gary
G
Entrican
Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos-Madrid 28130, Spain.
Noemí
N
Sevilla
MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, Scotland; massimo.palmarini@glasgow.ac.uk.
Massimo
M
Palmarini
D000820:Animal Diseases / Q000276:immunology* / Q000821:virology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001819:Bluetongue / Q000276:immunology / Q000821:virology; D001820:Bluetongue virus / Q000235:genetics / Q000276:immunology; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000378:metabolism; D042783:Endothelial Cells / Q000821:virology; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions / Q000276:immunology*; D007108:Immune Tolerance; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000821:virology; D012756:Sheep; D017154:Stromal Cells; D014766:Viremia / Q000276:immunology; D014774:Virulence; D014777:Virus Diseases / Q000662:veterinary*; D014780:Viruses / Q000235:genetics / Q000276:immunology*
arbovirus; bluetongue; follicular dendritic cells; immunosuppression; lymph node
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