Divergent Interactions ofEhrlichiachaffeensis-andAnaplasma phagocytophilum-InfectedLeukocytes with Endothelial CellBarriers

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Abstract
Human anaplasmosis (formerly human granulocytic ehrlichiosis) and human monocytic ehrlichiosis (HME) are emerging tick-borne infections caused by obligate intracellular bacteria in the familyAnaplasmataceae. Clinical findings include fever, headache, myalgia, leukopenia, thrombocytopenia, and hepatic inflammatory injury. WhereasEhrlichia chaffeensis(HME) often causes meningoencephalitis, this is rare withAnaplasma phagocytophiluminfection. The abilities of infected primary host monocytes and neutrophils and of infected HL-60 cells to cross human umbilical vein endothelial cell-derived EA.hy926 cell barriers and human brain microvascular cells (BMEC), a human blood-brain barrier model, were studied. Uninfected monocyte/macrophages crossed endothelial cell barriers six times more efficiently than neutrophils. MoreE. chaffeensis-infected monocytes transmigrated than uninfected monocytes, whereasA. phagocytophilumsuppressed neutrophil transmigration. Differences were not due to barrier dysfunction, as transendothelial cell resistivities were the same for uninfected cell controls. Similar results were obtained for HL-60 cells used as hosts forE. chaffeensisandA. phagocytophilum. Differential transmigration ofE. chaffeensis-andA. phagocytophilum-infected leukocytes and HL-60 cells confirmed a role for the pathogen in modifying cell migratory capacity. These results support the hypothesis thatAnaplasmataceaeintracellular infections lead to unique pathogen-specific host cell functional alterations that are likely important for pathogen survival, pathogenesis, and disease induction.