期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 41, 页码 E6238-E6247出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1610012113
关键词
arbovirus; immunosuppression; follicular dendritic cells; bluetongue; lymph node
资金
- Wellcome Trust [092806/Z/10/Z]
- W.B. Martin Scholarship
- Italian Ministry of Health
- Ministerio de Economia y Competitividad [AGL2012-33289]
- Comunidad de Madrid-Fondo Europeo de Desarrollo Regional [S2013/ABI-2906]
- Wellcome Trust [092806/Z/10/Z] Funding Source: Wellcome Trust
- MRC [MC_UU_12014/10] Funding Source: UKRI
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.
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