Passive immunization with anti-ActA and anti-listeriolysin O antibodies protects against Listeria monocytogenes infection in mice.

Krisana Asano,Hiroshi Sashinami,Shouhei Hirose,Dong-Liang Hu,Akio Nakane,Arihiro Osanai,Kouji Narita,Hisaya K Ono

doi:10.1038/srep39628

Krisana Asano, Hiroshi Sashinami + Show 6 more

Open Access

https://doi.org/10.1038/srep39628

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Journal: Scientific reports	Publication Date: Dec 1, 2016
Citations: 6	License type: CC BY 4.0

Affiliation: Hirosaki University, Kitasato University

Abstract

Listeria monocytogenes is an intracellular pathogen that causes listeriosis. Due to its intracellular niche, L. monocytogenes has evolved to limit immune recognition and response to infection. Antibodies that are slightly induced by listerial infection are completely unable to protect re-infection of L. monocytogenes. Thus, a role of antibody on the protective effect against L. monocytogenes infection has been neglected for a long time. In the present study, we reported that passive immunization with an excessive amount of antibodies against ActA and listeriolysin O (LLO) attenuates severity of L. monocytogenes infection. Combination of these antibodies improved survival of L. monocytogenes infected mice. Bacterial load in spleen and liver of listerial infected mice and infected RAW264.7 cells were significantly reduced by administration of anti-ActA and anti-LLO antibodies. In addition, anti-LLO antibody neutralized LLO activity and inhibited the bacterial escape from the lysosomal compartments. Moreover, anti-ActA antibody neutralized ActA activity and suppressed actin tail formation and cell-to-cell spread. Thus, our studies reveal that passive immunization with the excessive amount of anti-ActA and -LLO antibodies has potential to provide the protective effect against listerial infection.

Highlights

Listeria monocytogenes, a Gram-positive intracellular pathogen, is environmentally widespread and causes severe food-borne infections in humans and animals[1]
Specific antibodies against FbpA, p60, listeriolysin O (LLO), PI-PLC and ActA were prepared from rabbits
In comparison to normal rabbit globulin (NRG), survival of listerial infected mice was considerably improved by anti-ActA antibody as well as anti-LLO antibody but not by antiFbpA, p60 or PI-PLC antibody

Summary

Introduction

A Gram-positive intracellular pathogen, is environmentally widespread and causes severe food-borne infections in humans and animals[1]. To escape from phagocytic vacuoles, L. monocytogenes produces pore-forming listeriolysin O (LLO)[9] and phospholipase C (PI-PLC)[10,11] This bacterium produces ActA, a protein that is required for formation of actin rocket tails as well as for spread of bacteria from cell to cell[12]. Antibodies are well known to contribute to immune response against bacterial pathogens They neutralize their toxins, opsonize bacteria which promote uptake by phagocytic cells, and activate complements which enhance opsonization[17]. This study suggests that the conventional approach using antibodies to neutralize virulence factors may provide protection against listerial infections. Our studies reveal that anti-ActA and anti-LLO antibodies have a significant potential to protect L. monocytogenes infection

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Results

Conclusion