title: Thioredoxin 80-activated-monocytes (TAMs) inhibit the replication of intracellular pathogens.
abstract: BACKGROUND
  Thioredoxin 80 (Trx80) is an 80 amino acid natural cleavage product of Trx, produced primarily by monocytes. Trx80 induces differentiation of human monocytes into a novel cell type, named Trx80-activated-monocytes (TAMs).
  
  
  RESULTS
  In this investigation we present evidence for a role of TAMs in the control of intracellular bacterial infections. As model pathogens we have chosen Listeria monocytogenes and Brucella abortus which replicate in the cytosol and the endoplasmic reticulum respectively. Our data indicate that TAMs efficiently inhibit intracellular growth of both L. monocytogenes and B. abortus. Further analysis shows that Trx80 activation prevents the escape of GFP-tagged L. monocytogenes into the cytosol, and induces accumulation of the bacteria within the lysosomes. Inhibition of the lysosomal activity by chloroquine treatment resulted in higher replication of bacteria in TAMs compared to that observed in control cells 24 h post-infection, indicating that TAMs kill bacteria by preventing their escape from the endosomal compartments, which progress into a highly degradative phagolysosome.
  
  
  CONCLUSIONS
  Our results show that Trx80 potentiates the bactericidal activities of professional phagocytes, and contributes to the first line of defense against intracellular bacteria.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ximena
authors.initials: X
authors.lastname: Cortes-Bratti
authors.forename: Eugénie
authors.initials: E
authors.lastname: Bassères
authors.forename: Fabiola
authors.initials: F
authors.lastname: Herrera-Rodriguez
authors.forename: Silvia
authors.initials: S
authors.lastname: Botero-Kleiven
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Coppotelli
authors.forename: Jens B
authors.initials: JB
authors.lastname: Andersen
authors.forename: Maria G
authors.initials: MG
authors.lastname: Masucci
authors.forename: Arne
authors.initials: A
authors.lastname: Holmgren
authors.forename: Esteban
authors.initials: E
authors.lastname: Chaves-Olarte
authors.forename: Teresa
authors.initials: T
authors.lastname: Frisan
authors.forename: Javier
authors.initials: J
authors.lastname: Avila-Cariño
mesh_terms: D017848:Blood-Borne Pathogens / Q000187:drug effects; D002003:Brucella abortus / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D002451:Cell Compartmentation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000382:microbiology; D008089:Listeria monocytogenes / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D050296:Microbial Viability / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects*; D013879:Thioredoxins / Q000494:pharmacology*
chemical_list: D010446:Peptide Fragments; C427943:Trx80 protein, human; D013879:Thioredoxins