Effect of antibody on the Rickettsia-host cell interaction

Hui Min Feng, Ted Whitworth, Vsevolod Popov, David Walker

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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 N G-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.

Original languageEnglish (US)
Pages (from-to)3524-3530
Number of pages7
JournalInfection and Immunity
Volume72
Issue number6
DOIs
StatePublished - Jun 2004

Fingerprint

Rickettsia conorii
Rickettsia
Cell Communication
Antibodies
Macrophages
Monoclonal Antibodies
Tryptophan
Superoxide Dismutase
Antibody-Dependent Enhancement
Rickettsia Infections
Serum
omega-N-Methylarginine
Cell Line
Phagosomes
Immunoglobulin Fab Fragments
SCID Mice
Fc Receptors
Mannitol
Starvation
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Effect of antibody on the Rickettsia-host cell interaction. / Feng, Hui Min; Whitworth, Ted; Popov, Vsevolod; Walker, David.

In: Infection and Immunity, Vol. 72, No. 6, 06.2004, p. 3524-3530.

Research output: Contribution to journalArticle

Feng, Hui Min ; Whitworth, Ted ; Popov, Vsevolod ; Walker, David. / Effect of antibody on the Rickettsia-host cell interaction. In: Infection and Immunity. 2004 ; Vol. 72, No. 6. pp. 3524-3530.
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