Tissue Distribution of the Ehrlichia muris-Like Agent in a Tick Vector

Abstract

Human pathogens transmitted by ticks undergo complex life cycles alternating between the arthropod vector and a mammalian host. While the latter has been investigated to a greater extent, examination of the biological interactions between microbes and the ticks that carry them presents an equally important opportunity for disruption of the disease cycle. In this study, we used in situ hybridization to demonstrate infection by the Ehrlichia muris-like organism, a newly recognized human pathogen, of Ixodes scapularis ticks, a primary vector for several important human disease agents. This allowed us to assess whole sectioned ticks for the patterns of tissue invasion, and demonstrate generalized dissemination of ehrlichiae in a variety of cell types and organs within ticks infected naturally via blood feeding. Electron microscopy was used to confirm these results. Here we describe a strong ehrlichial affinity for epithelial cells, neuronal cells of the synganglion, salivary glands, and male accessory glands.

An Ixodes scapularis cell line with a predominantly neuron-like phenotype

“…Similarly, in ticks, Thogoto virus is maintained transstadially by infection of the synganglion (Booth et al 1989). The presence of numerous neuron-associated proteins in ISE6 may help explain why it is a popular host cell line for the study of neurotropic viruses or other intracellular pathogens with a propensity to infect nervous tissue, such as the Ehrlichia muris -like agent (Lynn et al 2015). …”

Proposal to reclassify Ehrlichia muris as Ehrlichia muris subsp. muris subsp. nov. and description of Ehrlichia muris subsp. eauclairensis subsp. nov., a newly recognized tick-borne pathogen of humans

“…E. muris has been found in Japan [17], Russia [14], Slovakia [12] and Korea [16], while EMLA strains, including Wisconsin T , have thus far been found only in Minnesota and Wisconsin in the Western Hemisphere [8][9][10]30]. Ixodes persulcatus and Haemaphysalis flava ticks serve as vectors of E. muris [12,31], whereas EMLA Wisconsin T is transmitted by I. scapularis [28,29,32]. It is also apparent that EMLA causes human disease, while it is not known whether E. muris AS145 T is a human pathogen, despite serological evidence of human exposure [31].…”

“…The target cell(s) in naturally infected vertebrate hosts is unknown; however, ehrlichiae can be found in mononuclear and endothelial cells of various organs and tissues in mice experimentally infected with this organism [28] E. muris subsp. eauclairensis is passaged transstadially in and transmitted by I. scapularis ticks [28,29,32] and the bacterium has been detected in or isolated from nymphal and adult stages [8][9][10]32]. In the tick, E. muris subsp.…”

“…In the tick, E. muris subsp. eauclairensis infects multiple cell types, particularly epithelial cells of the salivary glands, tracheae and male accessory glands, as well as neuronal cells of the synganglion [32]. The natural history of E. muris subsp.…”

“…Although bacteremia only occurs for a short time, multiple organs are infected, including the lungs, liver and spleen [28,29]. The bacteremia is sufficient for ehrlichial transmission to I. scapularis ticks through feeding in both C57BL/6 mice [28,29] and Syrian hamsters (Mesocricetus auratus) [32] and tick transmission may lead to mouse mortality [29]. A draft genome assembly for strain EmCRT is available (NCBI NZ_LANU01000000) consisting of 1.15 mb with 29.8 % GC.…”