Heat shock cognate protein 70 contributes to Brucella invasion into trophoblast giant cells that cause infectious abortion

Kenta Watanabe,Hidefumi Furuoka,Motohiro Horiuchi,Satoshi Tanaka,Masahisa Watarai,Masato Tachibana,Hiroshi Suzuki

doi:10.1186/1471-2180-8-212

Abstract

BackgroundThe cell tropism of Brucella abortus, a causative agent of brucellosis and facultative intracellular pathogen, in the placenta is thought to be a key event of infectious abortion, although the molecular mechanism for this is largely unknown. There is a higher degree of bacterial colonization in the placenta than in other organs and many bacteria are detected in trophoblast giant (TG) cells in the placenta. In the present study, we investigated mechanism of B. abortus invasion into TG cells.ResultsWe observed internalization and intracellular growth of B. abortus in cultured TG cells. A monoclonal antibody that inhibits bacterial internalization was isolated and this reacted with heat shock cognate protein 70 (Hsc70). Depletion and over expression of Hsc70 in TG cells inhibited and promoted bacterial internalization, respectively. IFN-γ receptor was expressed in TG cells and IFN-γ treatment enhanced the uptake of bacteria by TG cells. Administering the anti-Hsc70 antibody to pregnant mice served to prevent infectious abortion.ConclusionB. abortus infection of TG cells in placenta is mediated by Hsc70, and that such infection leads to infectious abortion.

Highlights

The cell tropism of Brucella abortus, a causative agent of brucellosis and facultative intracellular pathogen, in the placenta is thought to be a key event of infectious abortion, the molecular mechanism for this is largely unknown
We investigated the intracellular replication of B. abortus in trophoblast stem (TS) and trophoblast giant (TG) cells
SiRNA experiment The small interfering RNA (siRNA) duplexes used for silencing mouse heat shock cognate protein 70 (Hsc70), and βactin and AllStars Negative Control siRNA were purchased from QIGEN

Summary

Introduction

The cell tropism of Brucella abortus, a causative agent of brucellosis and facultative intracellular pathogen, in the placenta is thought to be a key event of infectious abortion, the molecular mechanism for this is largely unknown. Brucellosis is a widespread and economically important infectious disease of animals and humans caused by members of the genus Brucella. Brucella spp. are small gram-negative, facultative intracellular pathogens that cause abortion, retained placenta and infertility in numerous domestic and wild mammals, and a disease known as undulant fever in humans [1,2,3]. Transmission of Brucella spp. from infected animals to humans may be either direct or indirect. Direct transmission involves the respiratory, conjunctival and cutaneous routes, and is more important in people in close contact with infected animals. Brucella spp. occasionally causes spontaneous abortion in pregnant women [4]

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