TY - JOUR
T1 - Thioredoxin 80-activated-monocytes (TAMs) inhibit the replication of intracellular pathogens
AU - Cortes-Bratti, Ximena
AU - Bassères, Eugénie
AU - Herrera-Rodriguez, Fabiola
AU - Botero-Kleiven, Silvia
AU - Coppotelli, Giuseppe
AU - Andersen, Jens Bo
AU - Masucci, Maria G
AU - Holmgren, Arne
AU - Chaves-Olarte, Esteban
AU - Frisan, Teresa
AU - Avila-Cariño, Javier
PY - 2011
Y1 - 2011
N2 - 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). Principal Findings: 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. Significance: Our results show that Trx80 potentiates the bactericidal activities of professional phagocytes, and contributes to the first line of defense against intracellular bacteria.
AB - 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). Principal Findings: 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. Significance: Our results show that Trx80 potentiates the bactericidal activities of professional phagocytes, and contributes to the first line of defense against intracellular bacteria.
KW - Blood-Borne Pathogens
KW - Brucella abortus
KW - Cell Compartmentation
KW - Cell Division
KW - Cells, Cultured
KW - Colony Count, Microbial
KW - Down-Regulation
KW - Drug Evaluation, Preclinical
KW - Humans
KW - Intracellular Space
KW - Listeria monocytogenes
KW - Microbial Viability
KW - Monocytes
KW - Peptide Fragments
KW - Phagocytosis
KW - Thioredoxins
U2 - 10.1371/journal.pone.0016960
DO - 10.1371/journal.pone.0016960
M3 - Journal article
C2 - 21365006
SN - 1932-6203
VL - 6
SP - e16960
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 2
ER -