|
ИСТИНА |
Войти в систему Регистрация |
ИПМех РАН |
||
Deficiency of the B Cell-Activating Factor Receptor Results in Limited CD169+ Macrophage Function during Viral Infectionстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 9 октября 2015 г.
- Авторы: Xu HC, Huang J., Khairnar V., Duhan V., Pandyra AA, Grusdat M., Shinde P., McIlwain DR, Maney SK, Gommerman J., Löhning M., Ohashi PS, Mak TW, Pieper K., Sic H., Speletas M., Eibel H., Ware CF, Tumanov AV, Kruglov AA, Nedospasov SA, Häusinger D., Recher M., Lang KS, Lang PA
- Журнал: Journal of Virology
- Том: 89
- Номер: 9
- Год издания: 2015
- Издательство: American Society for Microbiology
- Местоположение издательства: United States
- Первая страница: 4748
- Последняя страница: 4759
- DOI: 10.1128/JVI.02976-14
- Аннотация: The B cell activating factor of the TNF family (BAFF) is critical for B-cell development and humoral immunity in mice and humans. While the role of BAFF in B cells has been widely described, its role in innate immunity remains unknown. Using BAFFR deficient mice we characterized BAFFR related innate and adaptive immune functions following infection with vesicular stomatitis virus (VSV) and lymphocytic choriomeningitis virus (LCMV). We identified a critical role for BAFFR signalling in the generation and maintenance of the CD169+ macrophage compartment. Consequently, Baffr-/- mice exhibited limited induction of innate type I interferon production after viral infection. Lack of BAFFR signalling reduced virus amplification and presentation following viral infection, resulting in highly reduced anti-viral adaptive immune responses. As a consequence, BAFFR deficient mice showed exacerbated and fatal disease after viral infection. Mechanistically, transient lack of B cells in Baffr-/- animals resulted in limited lymphotoxin expression, which was critical for maintenance of CD169+ cells. In conclusion, BAFFR signalling affects both innate and adaptive immune activation during viral infections. IMPORTANCE: Viruses cause acute and chronic infections in humans resulting in millions of deaths every year. Innate immunity is critical for the outcome of a viral infection. Innate type I interferon production can limit viral replication while adaptive immune priming by innate immune cells induces pathogen specific immunity with long term protection. Here we show that BAFFR deficiency not only perturbed B cells, but also resulted in limited CD169+ macrophages. These macrophages are critical in amplifying viral particles to trigger type I interferon production and initiate adaptive immune priming. Consequently, BAFFR deficiency resulted in reduced enforced viral replication, limited type I interferon production, and reduced adaptive immunity when compared to BAFFR competent controls. As a result, BAFFR deficient mice were predisposed to fatal viral infections. Thus, BAFFR expression is critical for innate immune activation and anti-viral immunity.
- Добавил в систему: Несмиянов Павел Павлович