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Publication : TNF receptor-associated factor 6-dependent CD40 signaling primes macrophages to acquire antimicrobial activity in response to TNF-alpha.

First Author  Andrade RM Year  2005
Journal  J Immunol Volume  175
Issue  9 Pages  6014-21
PubMed ID  16237096 Mgi Jnum  J:119350
Mgi Id  MGI:3701891 Doi  10.4049/jimmunol.175.9.6014
Citation  Andrade RM, et al. (2005) TNF receptor-associated factor 6-dependent CD40 signaling primes macrophages to acquire antimicrobial activity in response to TNF-alpha. J Immunol 175(9):6014-21
abstractText  IFN-gamma is considered an essential stimulus that allows macrophages to acquire activity against intracellular pathogens in response to a second signal such as TNF-alpha. However, protection against important pathogens can take place in the absence of IFN-gamma through mechanisms that are still dependent on TNF-alpha. Engagement of CD40 modulates antimicrobial activity in macrophages. However, it is not known whether CD40 can replace IFN-gamma as priming signal for induction of this response. We show that CD40 primes mouse macrophages to acquire antimicrobial activity in response to TNF-alpha. The effect of CD40 was not caused by modulation of IL-10 and TGF-beta production or TNFR expression and did not require IFN-alphabeta signaling. Induction of antimicrobial activity required cooperation between TNFR-associated factor 6-dependent CD40 signaling and TNFR2. These results support a paradigm where TNFR-associated factor 6 signaling downstream of CD40 alters the pattern of response of macrophages to TNF-alpha leading to induction of antimicrobial activity.
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