Deficiency of the B cell-activating factor receptor results in limited CD169+ macrophage function during viral infection

Haifeng C. Xu, Jun Huang, Vishal Khairnar, Vikas Duhan, Aleksandra A. Pandyra, Melanie Grusdat, Prashant Shinde, David R. McIlwain, Sathish Kumar Maney, Jennifer Gommerman, Max Löhning, Pamela S. Ohashi, Tak W. Mak, Kathrin Pieper, Heiko Sic, Matthaios Speletas, Hermann Eibel, Carl F. Ware, Alexei V. Tumanov, Andrey A. KruglovSergei A. Nedospasov, Dieter Häusinger, Mike Recher, Karl S. Lang, Philipp A. Lang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The B cell-activating factor (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 BAFF receptor (BAFFR)-deficient mice, we characterized BAFFR-related innate and adaptive immune functions following infection with vesicular stomatitis virus (VSV) and lymphocytic choriomeningitis virus (LCMV).Weidentified a critical role for BAFFR signaling 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 signaling reduced virus amplification and presentation following viral infection, resulting in highly reduced antiviral 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 is critical for maintenance of CD169+ cells. In conclusion, BAFFR signaling affects both innate and adaptive immune activation during viral infections.

Original languageEnglish (US)
Pages (from-to)4748-4759
Number of pages12
JournalJournal of virology
Volume89
Issue number9
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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