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Publication : B and T lymphocyte attenuator tempers early infection immunity.

First Author  Sun Y Year  2009
Journal  J Immunol Volume  183
Issue  3 Pages  1946-51
PubMed ID  19587015 Mgi Jnum  J:151703
Mgi Id  MGI:4355092 Doi  10.4049/jimmunol.0801866
Citation  Sun Y, et al. (2009) B and T lymphocyte attenuator tempers early infection immunity. J Immunol 183(3):1946-51
abstractText  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.
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