Oxidative stress responses in Ehrlichia-induced sepsis: mechanisms and implications in pathogenesis

埃里希氏体感染引起的脓毒症中的氧化应激反应:机制及其在发病机制中的意义

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Abstract

The host immune system uses reactive oxygen species (ROS) and reactive nitrogen species to build up an oxidative response as a host defense mechanism against infectious agents. However, uncontrolled ROS causes excessive inflammation and oxidative stress, which is counteracted by host antioxidant responses. Oxidative stress is recognized as an imbalance between the production of oxidants such as ROS and antioxidant defenses, which account for organ damage following severe infection with bacterial pathogens. Ehrlichia is an obligatory intracellular Gram-negative bacterial pathogen that causes human monocytic ehrlichiosis (HME), a potentially life-threatening tick-borne emerging infectious disease. Patients with severe HME develop sepsis that progresses to multi-organ failure. Ehrlichia develops several immune evasion strategies that cause oxidative stress and tissue damage. This review discusses various mechanisms that Ehrlichia employs to counteract host anti-oxidative responses, including the complex interplay among oxidative stress, mitochondrial damage, and endoplasmic stress during Ehrlichia-induced sepsis. Understanding these immune evasion strategies is important for the rational development of targeted therapy, not only for severe HME but also for other infectious and non-infectious diseases where oxidative stress is a key mechanism in pathogenesis.

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