Abstract
Scrub typhus is an understudied, potentially lethal disease caused by infection with Orientia tsutsugamushi. Despite causing an estimated 1 million cases per year and an increasing global presence, mechanisms of scrub typhus pathogenesis remain unclear. One of the most life-threatening conditions that can arise in scrub typhus patients is acute respiratory distress syndrome (ARDS). The development of ARDS is a complex process; some of its pathological hallmarks, including prolonged recruitment of inflammatory immune cells to the lung and vasculature damage, have been observed in humans and/or animal models of O. tsutsugamushi infection. Although different cell types and mechanisms may contribute to ARDS development during O. tsutsugamushi infection, this review highlights our current evidence of pulmonary endothelial activation and damage, the potential roles of neutrophils and macrophages in the lung, and the knowledge gaps in this field. Continued investigation of the lung microenvironment and cellular interactions will help elucidate disease pathogenesis and possible treatment during scrub typhus.
Highlights
The etiological agent of scrub typhus is Orientia tsutsugamushi, an obligate intracellular bacterium with unique biological features
We and other groups have recently established a number of murine models of O. tsutsugamushi infection mimicking severities of scrub typhus observed in humans (Keller et al, 2014; Shelite et al, 2014; Mendell et al, 2017)
While in vitro evidence exists for O. tsutsugamushi-induced activation of human endothelial cells (ECs) and cell death (Kim et al, 1999; Cho et al, 2001, 2010), there are no detailed reports for the mechanisms determining acute respiratory distress syndrome (ARDS) development in scrub typhus
Summary
The etiological agent of scrub typhus is Orientia tsutsugamushi, an obligate intracellular bacterium with unique biological features. We and other groups have recently established a number of murine models of O. tsutsugamushi infection mimicking severities of scrub typhus observed in humans (Keller et al, 2014; Shelite et al, 2014; Mendell et al, 2017).
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