Effect of antibody on the rickettsia-host cell interaction.
A recent study demonstrated that polyclonal antibodies to Rickettsia conorii and monoclonal antibodies to outer membrane proteins A (OmpA) and B (OmpB) provided effective, Fc-dependent, passive immunity, even in severe combined immunodeficient mice with an established infection. In order to determine the mechanism of protection, mouse endothelial and macrophage-like cell lines were infected with R. conorii that had been exposed to polyclonal antibodies, monoclonal antibodies to OmpA or OmpB, Fab fragments of the polyclonal antibodies, or normal serum or that were left untreated. At 0 h, Fc-dependent antibody enhancement of R. conorii adherence to endothelial and macrophage-like cell lines was inhibited by the presence of normal serum, suggesting Fc receptor-mediated adherence of opsonized rickettsiae. At 3 h, the opsonized rickettsiae had been internalized. After 72 h, inhibited survival of rickettsiae exposed to polyclonal antibodies or monoclonal antibodies to OmpA or OmpB was evident compared with growth of untreated and normal serum-treated and polyclonal Fab antibody-treated R. conorii. Polyclonal antibodies and an anti-OmpB monoclonal antibody inhibited the escape of R. conorii from the phagosome, resulting in intraphagolysosomal rickettsial death. At 48 h of infection, rickettsicidal activity of macrophages by opsonized rickettsiae was inhibited by NG-monomethyl-L-arginine, superoxide dismutase, mannitol, or supplemental L-tryptophan, and endothelial rickettsicidal activity against opsonized rickettsiae was inhibited by NG-monomethyl-L-arginine, superoxide dismutase, catalase, or supplemental L-tryptophan. Thus, Fc-dependent antibodies protected against R. conorii infection of endothelium and macrophages by opsonization that inhibited phagosomal escape and resulted in phagolysosomal killing mediated by nitric oxide, reactive oxygen intermediates, and L-tryptophan starvation.
Feng
Hui-Min
HM
Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas 77555-0609, USA.
Whitworth
Ted
T
Popov
Vsevolod
V
Walker
David H
DH
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D003600:Cytosol / Q000382:microbiology; D042783:Endothelial Cells / Q000276:immunology / Q000382:microbiology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D009895:Opsonin Proteins / Q000378:metabolism; D010588:Phagosomes / Q000382:microbiology; D011961:Receptors, Fc / Q000378:metabolism; D012282:Rickettsia Infections / Q000276:immunology / Q000517:prevention & control*; D020114:Rickettsia conorii / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology; D014709:Vero Cells
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D009895:Opsonin Proteins; D011961:Receptors, Fc; C078167:OMPA outer membrane proteins