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

Rosa M Andrade; Matthew Wessendarp; Jose-Andres C Portillo; Jun-Qi Yang; Francisco J Gomez; Joan E Durbin; Gail A Bishop; Carlos S Subauste

doi:10.4049/jimmunol.175.9.6014

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

Journal article

Peer reviewed

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

Rosa M Andrade, Matthew Wessendarp, Jose-Andres C Portillo, Jun-Qi Yang, Francisco J Gomez, Joan E Durbin, Gail A Bishop and Carlos S Subauste

The Journal of immunology (1950), Vol.175(9), pp.6014-6021

11/01/2005

DOI: 10.4049/jimmunol.175.9.6014

PMID: 16237096

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Abstract

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.

CD40 Antigens - physiology

TNF Receptor-Associated Factor 6 - physiology

Receptors, Tumor Necrosis Factor, Type II - physiology

Mice, Inbred C57BL

Transforming Growth Factor beta - biosynthesis

Tumor Necrosis Factor-alpha - pharmacology

Animals

CD40 Ligand - pharmacology

Female

Macrophages - drug effects

Signal Transduction - physiology

Mice

Mice, Inbred BALB C

Interferon-gamma - pharmacology

Macrophages - immunology

Details

Title: Subtitle: TNF receptor-associated factor 6-dependent CD40 signaling primes macrophages to acquire antimicrobial activity in response to TNF-alpha
Creators: Rosa M Andrade - Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Matthew Wessendarp
Jose-Andres C Portillo
Jun-Qi Yang
Francisco J Gomez
Joan E Durbin
Gail A Bishop
Carlos S Subauste
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.175(9), pp.6014-6021
DOI: 10.4049/jimmunol.175.9.6014
PMID: 16237096
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AI48406 / NIAID NIH HHS
Language: English
Date published: 11/01/2005
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984002383202771

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