title: Mycobacterium avium infection induces H-ferritin expression in mouse primary macrophages by activating Toll-like receptor 2.
abstract: Important for both host and pathogen survivals, iron is a key factor in determining the outcome of an infectious process. Iron with-holding, including sequestration inside tissue macrophages, is considered an important strategy to fight infection. However, for intra-macrophagic pathogens, such as Mycobacterium avium, host defence may depend on intracellular iron sequestration mechanisms. Ferritin, the major intracellular iron storage protein, plays a critical role in this process. In the current study, we studied ferritin expression in mouse bone marrow-derived macrophages upon infection with M. avium. We found that H-ferritin is selectively increased in infected macrophages, through an up-regulation of gene transcription. This increase was mediated by the engagement of Toll like receptor-2, and was independent of TNF-alpha or nitric oxide production. The formation of H-rich ferritin proteins and the consequent iron sequestration may be an important part of the panoply of antimicrobial mechanisms of macrophages.
authors.affiliation: IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal ; ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: Sandro
authors.initials: S
authors.lastname: Silva-Gomes
authors.affiliation: Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Centre de Recherche de Gif, Gif-sur-Yvette, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Bouton
authors.affiliation: IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal ; ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: Tânia
authors.initials: T
authors.lastname: Silva
authors.affiliation: San Raffaele Scientific Institute, DIBIT, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Santambrogio
authors.affiliation: IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal ; ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Rodrigues
authors.affiliation: IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal ; ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Appelberg
authors.affiliation: IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal ; ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: Maria Salomé
authors.initials: MS
authors.lastname: Gomes
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000235:genetics*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D051379:Mice; D009162:Mycobacterium avium; D009569:Nitric Oxide / Q000096:biosynthesis; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D001052:Apoferritins