Porcine CD18 mediates Actinobacillus pleuropneumoniae ApxIII species-specific toxicity.
Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia, produces Apx toxins that are recognized as major virulence factors. Recently, we showed that ApxIIIA-cytotoxic activity specifically targets Sus scrofa leukocytes. Since both LtxA from Aggregatibacter actinomycetem comitans (aggressive periodontitis in humans) and LktA from Mannheimia haemolytica (pneumonia in ruminants) share this characteristic, respectively towards human and ruminant leukocytes, and because both use the CD18 subunit to interact with their respective LFA-1, we hypothesized that ApxIIIA was likely to bind porcine CD18 to exercise its deleterious effects on pig leukocytes. A beta(2)-integrin-deficient ApxIIIA-resistant human erythroleukemic cell line was transfected either with homologous or heterologous CD11a/ CD18 heterodimers using a set of plasmids coding for human (ApxIIIA-resistant), bovine (-resistant) and porcine (-susceptible) CD11a and CD18 subunits. Cell preparations that switched from ApxIIIA-resistance to -susceptibility were then sought to identify the LFA-1 subunit involved. The results showed that the ApxIIIA-resistant recipient cell line was rendered susceptible only if the CD18 partner within the LFA-1 heterodimer was that of the pig. It is concluded that porcine CD18 is necessary to mediate A. pleuropneumoniae ApxIIIA toxin-induced leukolysis.
Vanden Bergh
Philippe G A C
PG
Department of Pathology, Faculty of Veterinary Medicine, University of Liege, Liège, Belgium.
Zecchinon
Laurent L M
LL
Fett
Thomas
T
Desmecht
Daniel
D
D016977:Actinobacillus pleuropneumoniae / Q000502:physiology*; D000818:Animals; D001426:Bacterial Proteins / Q000633:toxicity*; D040881:CD11a Antigen / Q000235:genetics / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D013045:Species Specificity; D013552:Swine
C079721:ApxIII toxin protein, Actinobacillus; D001426:Bacterial Proteins; D040881:CD11a Antigen; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1