Experimental infections of HL-60 cells with different strains of Anaplasma phagocytophilum isolated from humans, dogs and sheep

Abstract

[Objectives]: Anaplasma phagocytophilum is an intracellular rickettsial pathogen transmitted by Ixodes spp. ticks, causative agent of granulocytic anaplasmosis in humans, horses and dogs and tick-borne fever (TBF) in ruminants. In the United States, the number of cases of human granulocytic anaplasmosis (HGA) is increasing while TBF has not been reported. In Europe however, the prevalence of HGA is much lower compared to TBF in sheep. The focus of this research is to identify the source of these differences. [Method]: In the vertebrate host, A. phagocytophilum infects neutrophils and multiplies within a parasitophorous vacuole, thus evading host defenses. Previous research has shown that different strains of Anaplasma vary in their ability to infect and cause disease in different vertebrate hosts. Herein, we compared three strains of A. phagocytophilum isolated from humans, dogs and sheep, to experimentally infect the human promyelocytic cell line HL-60. Proteomics and transcriptomics analyses demonstrated differences and similarities in the modulation of different signalling pathways, supporting host-pathogen co-evolution. [Conclusions]: These results increase our understanding of the infection and pathogenic mechanisms of A. phagocytophilum in the vertebrate host and suggest mechanisms refining host-specificity of A. phagocytophilum strains that may contribute to the differences observed in disease prevalence in different regions