Journal article
Thioredoxin 80-Activated-Monocytes (TAMs) Inhibit the Replication of Intracellular Pathogens
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.
Language: | English |
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Publisher: | Public Library of Science |
Year: | 2011 |
Pages: | e16960 |
ISSN: | 19326203 , 15537358 and 1553734x |
Types: | Journal article |
DOI: | 10.1371/journal.pone.0016960 |
ORCIDs: | 0000-0003-1720-1581 |
Blood-Borne Pathogens Brucella abortus Cell Compartmentation Cell Division Cells, Cultured Colony Count, Microbial Down-Regulation Drug Evaluation, Preclinical Humans Intracellular Space Listeria monocytogenes Medicine Microbial Viability Monocytes Peptide Fragments Phagocytosis Q R Science Thioredoxins Trx80 protein, human