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Crohn's Disease Forum » Books, Multimedia, Research & News » Replication of Crohn's disease-associated AIEC within macrophages is dependent on TNF


08-06-2012, 11:40 PM   #1
kiny
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Replication of Crohn's disease-associated AIEC within macrophages is dependent on TNF

http://www.ncbi.nlm.nih.gov/pubmed/22042084

Replication of Crohn's disease-associated AIEC within macrophages is dependent on TNF-α secretion.

Adherent and invasive Escherichia coli (AIEC) associated with Crohn's disease are able to survive and to replicate extensively in active phagolysosomes within macrophages. AIEC-infected macrophages release large amounts of tumour necrosis factor-alpha (TNF-α) and do not undergo cell death. The aim of the present study was to determine what benefit AIEC bacteria could gain from inducing the release of large amounts of TNF-α by infected macrophages and to what extent the neutralization of TNF-α could affect AIEC intramacrophagic replication. Our results showed that the amount of TNF-α released by infected macrophages is correlated with the load of intramacrophagic AIEC bacteria and their intracellular replication. TNF-α secretion was not related to the number of bacteria entering host cells because when the number of bacteria internalized in macrophage was decreased by blocking lipid raft-dependent and clathrin-coated pits-dependent endocytosis, the amount of TNF-α secreted by infected macrophages was not modified. Interestingly, dose-dependent increases in the number of intracellular AIEC LF82 bacteria were observed when infected macrophages were stimulated with exogenous TNF-α, and neutralization of TNF-α secreted by AIEC-infected macrophages using anti-TNF-α antibodies induced a significant decrease in the number of intramacrophagic bacteria. These results indicate that AIEC bacteria use TNF-α as a Trojan horse to ensure their intracellular replication because replication of AIEC bacteria within macrophages induces the release of TNF-α, which in turn increases the intramacrophagic replication of AIEC. Neutralizing TNF-α secreted by infected macrophages may represent an effective strategy to control AIEC intracellular replication.
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