Disease relevance of Anaplasma phagocytophilum

• A human granulocytic ehrlichiosis (HGE) agent with 16S rDNA sequence identical to the published sequence of HGE agents was isolated from a patient from New York State by inoculation of the blood leukocyte fraction directly into a human promyelocytic leukemia cell line HL-60 [1].
• The HGE agent was resistant to clindamycin, trimethoprim-sulfamethoxazole, and imipenem-cilastatin, as well as to ampicillin, ceftriaxone, erythromycin, and azithromycin, antibiotics commonly used to treat Lyme disease [2].
• When the encoded protein, named AnkA, was expressed in Escherichia coli, it was recognized by antibodies from rabbits and mice immunized with the HGE agent, sera from humans convalescent from HGE, and sera from horses convalescent from HGE and E. equi infection [3].
• Infection with both E. chaffeensis and E. sennetsu, but not HGE agent, in the acute monocytic leukemia cell line THP-1 almost completely inhibited by treatment with deferoxamine, a cell-permeable iron chelator [4].
• Production of tumour necrosis factor-alpha (TNF-alpha) and reactive nitrogen intermediates by ovine peripheral blood leucocytes stimulated by Ehrlichia (Cytoecetes) phagocytophila [5].

High impact information on Anaplasma phagocytophilum

• These findings showed that p44 multigenes have several active expression sites and the expression is regulated at transcriptional level, suggesting a potentially unique mechanism for generating the diversity in major antigenic outer membrane proteins of the HGE agent [6].
• We previously cloned a gene encoding HGE agent 44-kDa major outer membrane protein and designated it p44 [6].
• The present study provides new information for understanding the role of the p44 multigene family in transmission of the HGE agent between mammals and ticks [7].
• Among PBLs, neutrophils and lymphocytes expressed IL-1beta mRNA but not TNF-alpha or IL-6 mRNA in response to the HGE agent, whereas monocytes expressed all three of these cytokine mRNAs [8].
• Expression of IL-8, IL-10, gamma interferon, transforming growth factor beta, and IL-2 mRNAs in response to the HGE agent was not remarkable [8].

Chemical compound and disease context of Anaplasma phagocytophilum

• Addition of oxytetracycline, however, did not prevent or reverse the antiapoptotic effect of the HGE agent [9].
• MG-132, a proteasome inhibitor, and cycloheximide accelerated the apoptosis of neutrophils and overrode the antiapoptotic effect of the HGE agent [9].
• Treatment of neutrophils with a transglutaminase inhibitor, monodansylcadaverine, blocked the antiapoptotic effect of the HGE agent [9].
• The HGE agent induced expression of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and IL-6 mRNAs and proteins in PBLs in a dose-dependent manner to levels as high as those resulting from Escherichia coli lipopolysaccharide stimulation [8].
• Prophylactic use of long-acting tetracycline against tick-borne fever (Cytoecetes phagocytophila) in sheep [10].

Biological context of Anaplasma phagocytophilum

• These observations suggest that induction of proinflammatory-cytokine gene expression by the major outer membrane protein of the HGE agent in monocytes, which are not the primary host cells of the HGE agent, contributes to HGE pathogenesis and immunomodulation [8].
• The 16S ribosomal DNA sequence of the isolate was determined to be identical to that of the HGE agent [11].
• Southern blot results revealed the existence of multigenes homologous to the P44 gene in the genome of the HGE agent [12].
• To assay the prevalence of the HGE agent in vector ticks, we screened 818 individual I. scapularis from 15 locations in South Carolina, Georgia, and Florida using nested polymerase chain reaction, which targets the HGE agent 16S rRNA gene [13].

Anatomical context of Anaplasma phagocytophilum

• In contrast, HGE agent in THP-1 or HL-60 cells induced no increase in TfR mRNA levels [4].

Gene context of Anaplasma phagocytophilum

• These data demonstrate that the HGE agent elicits a prominent IFN-gamma response in mice and that IFN-gamma is important in controlling the degree of rickettsemia during the early phase of infection, while IFN-gamma independent mechanisms play a role at later time points [14].
• However, HGE agent infection had no effect on IRP-1 binding activity [4].
• The percent identities of the gltA nucleotide sequences among ehrlichial species were 49.7% (E. risticii versus A. centrale) to 99.8% (HGE agent versus E. equi) [15].
• Sera were obtained from 18 patients with HGE, mostly within the first 6 weeks of clinical infection, and from mice infected with the HGE agent for up to 3 weeks [16].
• Of the seropositive patients, HGE agent DNA was detected by polymerase chain reaction in the first serum from 4 of 5 patients and was present in the serum of 1 of 2 untreated patients after 21 days, even when E. equi antibodies also were present [17].

Analytical, diagnostic and therapeutic context of Anaplasma phagocytophilum

• Western blot results with the OMP fraction of the six isolates were consistent with results with the whole HGE agent [18].
• Previous serologic studies in patients with a diagnosis of Lyme borreliosis indicate that HGE may exist in Europe. We report the first documented case of HGE in Europe. The diagnosis was established by seroconversion to E. equi and the HGE agent and by PCR with sequence analysis of the gene encoding the HGE agent 16S rRNA [19].

References