Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae) is an obligate intracellular tick-borne pathogen that causes human granulocytic anaplasmosis (HGA), tick-borne fever of ruminants, and equine and canine granulocytic anaplasmosis . HGA, first described in 1994 in the United States, has become a predominant form of anaplasmosis and among the most common tick-borne pathogens in the United States and Europe . HGA is characterized by fever, headache, myalgia, and malaise, as well as leukopenia, thrombocytopenia, and elevated levels of C-reactive protein and liver transaminases, which are indicators of inflammatory response and hepatic injury, respectively . Although the disease is usually self-limiting, severe complications can result, including prolonged fever, shock, seizures, pneumonitis, acute renal failure, hemorrhage, rhabdomyolysis, opportunistic infections and death .
A. phagocytophilum initiates infection of polymorphonuclear leucocytes by adhesion to host cells, a process which involves adhesins, such as the human P-selectin glycoprotein ligand-1 (PSGL-1) that bind cooperatively to neutrophil ligand molecules . After infection, A. phagocytophilum undergoes a developmental cycle in parasitophorous vacuoles that includes reticulated and dense forms, and this infection modulates host cell growth and differentiation .
While the main vector for A. phagocytophilum are tick species belonging to the Ixodes ricinus complex, the pathogen multiplies in a broad range of terrestrial vertebrates [2, 4]. In the laboratory, A. phagocytophilum can be propagated in undifferentiated human promyelocytic HL-60 cells. Infection of HL-60 cells with A. phagocytophilum results in modulation of host cell gene expression (see for example [5, 6].
Sp110 is a member of the nuclear body (NB) components that functions as a nuclear hormone receptor transcriptional coactivator . Sp110 and other NB-associated proteins, induced by type I (α/β) and type II (γ) interferons (IFNs), play a role in IFN response and virus replication . Sp110 expression is induced in human peripheral blood leukocytes and spleen but not in other tissues . Sp110 inhibits vesicular stomatitis virus and influenza virus replication, confers resistance to human Foamy virus, and gene polymorphisms or mutations have been associated with susceptibility to the Hepatitis C virus and immunodeficiency and hepatic veno-occlusive disease [8–10].
Recently, the mouse Sp110 homologue, the intracellular pathogen resistance 1 (Ipr1) gene, was shown to control susceptibility to Mycobacterium tuberculosis in mice . As in mice, Ipr1-like expression was higher in European wild boar resistant to natural M. bovis infection . Pan et al.  proposed that Ipr1-related proteins may play a role in integrating signals generated by intracellular pathogens or viruses with host cell mechanisms that regulate gene expression and cell death, thus modulating host susceptibility to infection. However, recent publications have documented that polymorphisms in Sp110 gene are not associated with susceptibility to tuberculosis in humans [13–15]. These results suggest that Sp110 may have a different role during infection by intracellular bacterial pathogens in humans.
In the study reported herein, we hypothesized that Sp110 may be involved in the infection of human promyelocytic cells with A. phagocytophilum and used a combination of real-time RT-PCR and RNA interference (RNAi) to test this hypothesis.