Anthrax oedema toxin induces anthrax toxin receptor expression in monocyte-derived cells.
Bacillus anthracis, the causative agent of anthrax, secretes two bipartite toxins that help the bacterium evade the immune system and contribute directly to pathogenesis. Both toxin catalytic moieties, lethal factor (LF) and oedema factor (OF), are internalized into the host-cell cytosol by a third factor, protective antigen (PA), which binds to cellular anthrax toxin receptors (ANTXRs). Oedema factor is an adenylate cyclase that impairs host defences by raising cellular cAMP levels. Here we demonstrate that oedema toxin (PA + OF) induces an increase in ANTXR expression levels in macrophages and dendritic cells resulting in an increased rate of toxin internalization. Furthermore, we show that increases in ANTXR mRNA levels depends on the ability of OF to increase cAMP levels, is mediated through protein kinase A-directed signalling and is monocyte-lineage-specific. To our knowledge, this is the first report of a bacterial toxin inducing host target cells to increase toxin receptor expression.
Maldonado-Arocho
Francisco J
FJ
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Fulcher
Jennifer A
JA
Lee
Benhur
B
Bradley
Kenneth A
KA
D000262:Adenylyl Cyclases / Q000494:pharmacology*; D000818:Animals; D000942:Antigens, Bacterial / Q000187:drug effects / Q000378:metabolism; D001427:Bacterial Toxins / Q000378:metabolism; D019070:Cell Lineage; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008840:Microfilament Proteins; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D009363:Neoplasm Proteins / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*
C473287:ANTXR1 protein, human; C447150:ANTXR2 protein, human; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C030325:anthrax toxin; C070309:anthrax toxin receptors; D000262:Adenylyl Cyclases