Cellular and Systemic Interactions of Orientia tsutsugamushi with Mammalian Host

Se-Yoon Kim; Myung-Sik Choi; Nam-Hyuk Cho

doi:10.4167/jbv.2012.42.4.276

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Kim, Choi, and Cho: Cellular and Systemic Interactions of Orientia tsutsugamushi with Mammalian Host

Review Article

Journal of Bacteriology and Virology

Journal of Bacteriology and Virology 2012; 42(4): 276-283.

Published online: 24 December 2012

DOI: https://doi.org/10.4167/jbv.2012.42.4.276

Cellular and Systemic Interactions of Orientia tsutsugamushi with Mammalian Host

Se-Yoon Kim, Myung-Sik Choi, Nam-Hyuk Cho

Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea.

Corresponding author: Nam-Hyuk Cho. Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Korea. Phone: +82-2-740-8392, Fax: +82-2-743-0881, chonh@snu.ac.kr

Received 2 October 2012 Revised 26 October 2012 Accepted 30 October 2012

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/license/by-nc/3.0/).

Abstract

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi infection and one of main causes of febrile illness in the Asia-Pacific region. It has been estimated that one billion people are at risk and one million new cases arise each year in the endemic region. Despite of aggressive attempts to develop a prophylactic vaccine against scrub typhus during last several decades, all approaches have failed to generate long lasting immunity. In addition, little is known about the immunological pathogenesis of scrub typhus. In this review, we summarized recent findings of cellular and systemic interaction of O. tsutsugamushi with mammalian host, especially focusing on the molecular basis of intracellular invasion and immunological changes observed during the bacterial infection.

Keywords: Orientia tsutsugamushi, Scrub typhus, Immune responses, Intracellular invasion

Figures and Tables

Figure 1

Hypothetical model for the intracellular invasion of O. tsutsugamushi. O. tsutsugamushi (OT) surface molecules (e.g., TSA56 and ScaC) mediate bacterial adhesion to host cells by binding to host-specific receptors, such as Syndecan-4 and fibronectin. The interaction between O. tsutsugamushi and fibronectin may mediate the engagement of integrins, which subsequently may activate downstream signaling molecules, such as FAK, Src kinase, and RhoA GTPase. Signaling adapters, such as talin and paxillin, are recruited to the site of infection. These signaling events consequently induce the internalization of O. tsutsugamushi into non-phagocytic host cells, which involves the clathrin-mediated endocytic pathway. The bacteria subsequently travel through the early and late endosomes and escape from the endosomal compartment within 2 h after infection. Cytosolic O. tsutsugamushi might move to microtubule organizing center via trafficking thorough microtubules and replicates in the perinuclear region (24).

Table 1

Summary of leukocyte changes observed during acute and convalescent phase of scrub typhus (52).

Notes

This study was supported by grants (A111503) from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea.

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