Tumor necrosis factormediated survival of CD169+ cells promotes immune activation during vesicular stomatitis virus infection

Prashant V. Shinde, Haifeng C. Xu, Sathish Kumar Maney, Andreas Kloetgen, Sukumar Namineni, Yuan Zhuang, Nadine Honke, Namir Shaabani, Nicolas Bellora, Mareike Doerrenberg, Mirko Trilling, Vitaly I. Pozdeev, Nico van Rooijen, Stefanie Scheu, Klaus Pfeffer, Paul R. Crocker, Masato Tanaka, Sujitha Duggimpudi, Percy Knolle, Mathias HeikenwalderJ. rgen Ruland, Tak W. Mak, Dirk Brenner, Aleksandra A. Pandyra, Jessica I. Hoell, Arndt Borkhardt, Dieter Häussinger, Karl S. Lang, Philipp A. Lang

Research output: Contribution to journalArticleAcademicpeer-review


Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169+ cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169+ cells during viral infections remain unclear. Here, we show that tumor necrosis factor is produced by CD11b+ Ly6C+ Ly6G+ cells following infection with VSV. The absence of TNF or TNF receptor 1 (TNFR1) resulted in reduced numbers of CD169+ cells and in reduced type I interferon (IFN-I) production during VSV infection, with a severe disease outcome. Specifically, TNF triggered RelA translocation into the nuclei of CD169+ cells; this translocation was inhibited when the paracaspase MALT-1 was absent. Consequently, MALT1 deficiency resulted in reduced VSV replication, defective innate immune activation, and development of severe disease. These findings indicate that TNF mediates the maintenance of CD169+ cells and innate and adaptive immune activation during VSV infection.
Original languageEnglish
Article numbere01637-17
JournalJournal of Virology
Issue number3
Publication statusPublished - 2018

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