An animal model of a newly emerging human ehrlichiosis

Ehrlichioses are emerging tick-borne diseases that affect several mammals, including humans. The genus Ehrlichia comprises Ehrlichia chaffeensis, Ehrlichia canis, Ehrlichia ewingii, Ehrlichia ruminantium, Panola Mountain Ehrlichia, and Ehrlichia muris; however, a new species closely related to E. muris, designated E. muris–like agent (EMLA), has been identified in human patients and ticks [1, 2]. All ehrlichial species except E. muris have been reported to cause infection in humans, which can lead to life-threatening disease, such as human monocytotropic ehrlichiosis (HME) caused by E. chaffeensis [2–6]. E. chaffeensis infection does not provide a relevant animal model, since it does not induce progressive infection in laboratory animals. E. chaffeensis infection in immunocompromised mice with severe combined immunodeficiency does not provide an ideal model for studying pathogenesis or immunity. Other murine models have been developed to better understand the mechanisms of ehrlichial infection and disease mechanisms: E. muris, a nonlethal agent inducing persistent infection, and Ixodes ovatus Ehrlichia (IOE), a lethal model [7, 8]. IOE has been detected only in I. ovatus ticks in Japan [9]. EMLA has been detected in patients from the upper Midwestern United States since 2009 [2]. The new bacterium has been identified in different stages of Ixodes scapularis ticks collected from the same region as the human patients. The disease caused by EMLA is similar to E. chaffeensis infection, with fever, malaise, fatigue, headache, nausea, and vomiting. Clinical laboratory findings include elevated hepatic aminotransferase levels, thrombocytopenia, and lymphopenia [2, 10]. An ideal animal model to study monocytotropic ehrlichiosis infection should use a human pathogen and induce dose-dependent sublethal and lethal infection [11–13]. The objective of this research was to develop and characterize a better mouse model of human ehrlichiosis, using EMLA, which will be used for future studies of the vector-host-pathogen interaction, ehrlichial pathogenesis, and immunity.