title: Exposure to anthrax toxin alters human leucocyte expression of anthrax toxin receptor 1.
abstract: Anthrax is a toxin-mediated disease, the lethal effects of which are initiated by the binding of protective antigen (PA) with one of three reported cell surface toxin receptors (ANTXR). Receptor binding has been shown to influence host susceptibility to the toxins. Despite this crucial role for ANTXR in the outcome of disease, and the reported immunomodulatory consequence of the anthrax toxins during infection, little is known about ANTXR expression on human leucocytes. We characterized the expression levels of ANTXR1 (TEM8) on human leucocytes using flow cytometry. In order to assess the effect of prior toxin exposure on ANTXR1 expression levels, leucocytes from individuals with no known exposure, those exposed to toxin through vaccination and convalescent individuals were analysed. Donors could be defined as either 'low' or 'high' expressers based on the percentage of ANTXR1-positive monocytes detected. Previous exposure to toxins appears to modulate ANTXR1 expression, exposure through active infection being associated with lower receptor expression. A significant correlation between low receptor expression and high anthrax toxin-specific interferon (IFN)-γ responses was observed in previously infected individuals. We propose that there is an attenuation of ANTXR1 expression post-infection which may be a protective mechanism that has evolved to prevent reinfection.
authors.affiliation: Section of Infectious Diseases and Immunity, Department of Medicine Imperial College, Hammersmith Hospital, London.
authors.forename: R J
authors.initials: RJ
authors.lastname: Ingram
authors.forename: A
authors.initials: A
authors.lastname: Harris
authors.forename: S
authors.initials: S
authors.lastname: Ascough
authors.forename: G
authors.initials: G
authors.lastname: Metan
authors.forename: M
authors.initials: M
authors.lastname: Doganay
authors.forename: L
authors.initials: L
authors.lastname: Ballie
authors.forename: E D
authors.initials: ED
authors.lastname: Williamson
authors.forename: H
authors.initials: H
authors.lastname: Dyson
authors.forename: J H
authors.initials: JH
authors.lastname: Robinson
authors.forename: S
authors.initials: S
authors.lastname: Sriskandan
authors.forename: D M
authors.initials: DM
authors.lastname: Altmann
mesh_terms: D000881:Anthrax / Q000097:blood* / Q000235:genetics; D022122:Anthrax Vaccines / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000378:metabolism / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D015331:Cohort Studies; D003289:Convalescence; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008840:Microfilament Proteins; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D017192:Skin Diseases, Bacterial / Q000097:blood* / Q000235:genetics; D014421:Turkey; D006113:United Kingdom; D014611:Vaccination
chemical_list: C473287:ANTXR1 protein, human; D022122:Anthrax Vaccines; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; C030325:anthrax toxin; D007371:Interferon-gamma