Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression

Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):E6238-E6247. doi: 10.1073/pnas.1610012113. Epub 2016 Sep 26.

Abstract

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.

Keywords: arbovirus; bluetongue; follicular dendritic cells; immunosuppression; lymph node.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Diseases / immunology*
  • Animal Diseases / virology
  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Bluetongue / immunology
  • Bluetongue / virology
  • Bluetongue virus / genetics
  • Bluetongue virus / immunology
  • Dendritic Cells, Follicular / immunology*
  • Dendritic Cells, Follicular / metabolism
  • Endothelial Cells / virology
  • Gene Expression Regulation, Viral
  • Host-Pathogen Interactions / immunology*
  • Immune Tolerance*
  • Immunohistochemistry
  • Lymph Nodes / immunology
  • Macrophages / immunology
  • Macrophages / virology
  • Sheep
  • Stromal Cells
  • Viremia / immunology
  • Virulence
  • Virus Diseases / veterinary*
  • Viruses / genetics
  • Viruses / immunology*