Anti-LcrV Antibody Inhibits Delivery of Yops by Yersinia pestis KIM5 by Directly Promoting Phagocytosis

Abstract

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Yersinia pestisCan Bypass Protective Antibodies to LcrV and Activation with Gamma Interferon To Survive and Induce Apoptosis in Murine Macrophages

“…Opsonization with anti-LcrV antibodies increases the phagocytosis of Y. pestis by macrophages (10,29,43). The increased phagocytosis of Y. pestis mediated by anti-LcrV antibody opsonization is associated with reduced Yop translocation (10,29) and reduced apoptosis (10,29,43).…”

“…The growth of Y. pestis at 37°C prior to infection promotes Yop delivery during phagocytosis, and as a result, the efficiency of bacterial uptake by macrophages is reduced. However, ϳ20 to 35% of 37°C-grown Y. pestis bacteria that associate with macrophages are internalized (10,43). Yop-expressing Y. pestis that are internalized by naïve macrophages are able to survive intracellularly (21).…”

“…Opsonization with anti-LcrV antibodies increases the phagocytosis of Y. pestis by macrophages (10,29,43). The increased phagocytosis of Y. pestis mediated by anti-LcrV antibody opsonization is associated with reduced Yop translocation (10,29) and reduced apoptosis (10,29,43). The ability of anti-LcrV antibodies to inhibit apoptosis in macrophages infected with Y. pestis is commonly used as a measure of neutralizing activity (3,(43)(44)(45).…”

Yersinia pestisbiovarMicrotusstrain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques

“…LcrV is a multifunctional protein secreted by the type III system, which both forms the translocation pore at the tip of the surfaceexposed needle and provides protective immunity to Y. pestis infections. [43][44][45][46][47] Although V-antigen is a surface-exposed protein, it is only localized at the tip of the needle and is not secreted as much as F1-antigen. This may explain why only a small amount of antibody to V-antigen is produced in animals immunized with the EV and the Y. pestis strain 201.…”

Diminished LcrV Secretion Attenuates Yersinia pseudotuberculosis Virulence

“…From here, LcrV promotes assembly of the translocon pore in the eukaryotic cell plasma membrane (6,15,27). Since antibodies specific for LcrV also prevent effector translocation and protect animals from challenge with virulent yersiniae (8,18,32,62), LcrV is being pursued as a vaccine candidate against plague and other Yersinia infections (59). LcrV also impacts the positive regulatory loop needed for Yop synthesis.…”