title: Replication of Crohn's disease-associated AIEC within macrophages is dependent on TNF-α secretion.
abstract: 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.
authors: Clermont Université, Université d'Auvergne, JE2526, Clermont-Ferrand, France.
authors: Marie-Agnès
authors: MA
authors: Bringer
authors: Elisabeth
authors: E
authors: Billard
authors: Anne-Lise
authors: AL
authors: Glasser
authors: Jean-Frédéric
authors: JF
authors: Colombel
authors: Arlette
authors: A
authors: Darfeuille-Michaud
mesh_terms: D000818:Animals; D002460:Cell Line; D003424:Crohn Disease / Q000382:microbiology*; D004705:Endocytosis; D054308:Enteropathogenic Escherichia coli / Q000502:physiology*; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha