B and T lymphocyte attenuator tempers early infection immunity

Yonglian Sun, Nicholas K. Brown, Matthew J. Ruddy, Mendy L. Miller, Youjin Lee, Yang Wang, Kenneth M. Murphy, Klaus Pfeffer, Lieping Chen, Jonathan Kaye, Yang Xin Fu

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38 Scopus citations

Abstract

Coinhibitory pathways are thought to act in later stages of an adaptive immune response, but whether coinhibition contributes to early innate immunity is unclear. We show that engagement of the newly discovered coinhibitory receptor B and T lymphocyte attenuator (BTLA) by herpesvirus entry mediator (HVEM) is critical for negatively regulating early host immunity against intracellular bacteria. Both HVEM-/- and BTLA-/-, but not LIGHT-/-, mice are more resistant to listeriosis compared with wild-type mice, and blockade of the BTLA pathway promotes, while engagement inhibits, early bacterial clearance. Differences in bacterial clearance were seen as early as 1 day postinfection, implicating the initial innate response. Therefore, innate cell function in BTLA-/- mice was studied. We show that innate cells from BTLA-/- mice secrete significantly more proinflammatory cytokines upon stimulation with heat-killed Listeria. These results provide the first evidence that a coinhibitory pathway plays a critical role in regulating early host innate immunity against infection.

Original languageEnglish (US)
Pages (from-to)1946-1951
Number of pages6
JournalJournal of Immunology
Volume183
Issue number3
DOIs
StatePublished - Aug 1 2009

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Sun, Y., Brown, N. K., Ruddy, M. J., Miller, M. L., Lee, Y., Wang, Y., Murphy, K. M., Pfeffer, K., Chen, L., Kaye, J., & Fu, Y. X. (2009). B and T lymphocyte attenuator tempers early infection immunity. Journal of Immunology, 183(3), 1946-1951. https://doi.org/10.4049/jimmunol.0801866