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Home / Equine Research Bank / Clin Vaccine Immunol / Sequential analysis of Anaplasma phagocytophilum msp2 transc...
Clinical and vaccine immunology : CVI2007; 15(3); 418-424; doi: 10.1128/CVI.00417-07

Sequential analysis of Anaplasma phagocytophilum msp2 transcription in murine and equine models of human granulocytic anaplasmosis.

Abstract: Anaplasma phagocytophilum causes human granulocytic anaplasmosis by inducing immunopathologic responses. Its immunodominant Msp2 protein is encoded by a family of >100 paralogs. Msp2 (msp2) expression modulates in the absence of immune pressure, and prolonged in vitro passage modulates in vivo virulence. Because programmed MSP2 expression occurs in Anaplasma marginale, we hypothesized a similar event in A. phagocytophilum in vivo, with specific Msp2 expression triggering immunopathologic injury or clinical manifestations of disease. We examined msp2 transcripts in 11 B6 mice and 6 horses inoculated with low- or high-passage A. phagocytophilum Webster strain. Blood was sequentially obtained through 3 weeks postinfection for msp2 reverse transcription-PCR. Horses were additionally assessed for clinical manifestations, seroconversion, complete blood count, blood chemistry, and cytokine gene transcription. In both species, there was no consistent emergence of msp2 transcripts, and all 22 msp2 variants were detected in both passage groups. Clinical severity was much higher for high-passage-infected than for low-passage-infected horses, preceded by higher levels of blood gamma interferon transcription on day 7. Antibody was first detected on day 7, and all horses seroconverted by day 22, with a trend toward lower antibody titers in low-passage-infected animals. Leukocyte and platelet counts were similar between experimental groups except on day 13, when low-passage-infected animals had more profound thrombocytopenia. These findings corroborate studies with mice, where msp2 diversity did not explain differences in hepatic histopathology, but differ from the paradigm of low-passage A. phagocytophilum causing more significant clinical illness. Alteration in transcription of msp2 has no bearing on clinical disease in horses, suggesting the existence of a separate proinflammatory component differentially expressed with changing in vitro passage.
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Publication Date: 2007-12-19 PubMed ID: 18094110PubMed Central: PMC2268257DOI: 10.1128/CVI.00417-07Google Scholar: Lookup
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  • Journal Article
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  • N.I.H.
  • Extramural

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research focuses on the study of Anaplasma phagocytophilum, a bacteria that causes human granulocytic anaplasmosis, by analyzing the transcription of its Msp2 protein in murine and equine models. The study aimed to investigate if specific expression of Msp2 protein impacts the severity and symptoms of the disease.

Research Methodology

  • The study was conducted on 11 B6 mice and 6 horses, which were inoculated with either low- or high-passage A. phagocytophilum Webster strain.
  • The researchers studied the msp2 transcript, which is responsible for the Msp2 protein production, over a period of three weeks post-infection. This was performed using msp2 reverse transcription-PCR.
  • Additionally, horses were assessed for clinical manifestations, seroconversion (the time period during which a specific antibody develops and becomes detectable in the blood), complete blood count, blood chemistry, and cytokine (a type of protein) gene transcription.

Observations from the Study

  • There was no consistent emergence of msp2 transcripts in either the mice or the horses during the research period.
  • All 22 msp2 variants were detected in both passage groups, implying that both strains exhibited the same level of msp2 transcript diversity.
  • Clinical severity was found to be significantly higher in high-passage-infected horses than in those infected with the low-passage strain.
  • A higher level of blood gamma interferon transcription was observed during the earlier stage of infection in the more severely affected horses.
  • Antibodies were first detected on day 7, and all horses were found to have developed detectable antibodies by day 22. In addition, horses infected with the low-passage strain tended to have lower antibody titers.
  • Leukocyte and platelet counts were similar between groups, with the exception of day 13, on which low-passage-infected animals had a significantly lower platelet count, an indication of a more severe infection.

Conclusions

  • The study concluded that the diversity of msp2 did not explain the differences in pathology associated with the disease, a result that aligns with previous studies on mice.
  • It contradicts, however, the concept of low-passage A. phagocytophilum causing more significant clinical illness. Researchers stated that alteration in transcription of msp2, whether from low or high passage, did not affect the severity of clinical disease in horses.
  • Thus, the study suggests there might exist a different proinflammatory component whose expression changes with different levels of in vitro passages and impacts the clinical manifestations of the disease.

Cite This Article

APA
Scorpio DG, Leutenegger C, Berger J, Barat N, Madigan JE, Dumler JS. (2007). Sequential analysis of Anaplasma phagocytophilum msp2 transcription in murine and equine models of human granulocytic anaplasmosis. Clin Vaccine Immunol, 15(3), 418-424. https://doi.org/10.1128/CVI.00417-07

Publication

Clinical and vaccine immunology : CVI
ISSN: 1556-679X
NlmUniqueID: 101252125
Country: United States
Language: English
Volume: 15
Issue: 3
Pages: 418-424

Researcher Affiliations

Scorpio, Diana G
  • Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. dscorpio@jhmi.edu
Leutenegger, Christian
    Berger, Jeannine
      Barat, Nicole
        Madigan, John E
          Dumler, J Stephen

            MeSH Terms

            • Anaplasma phagocytophilum / genetics
            • Anaplasma phagocytophilum / immunology
            • Anaplasma phagocytophilum / metabolism
            • Anaplasma phagocytophilum / pathogenicity
            • Animals
            • Antibodies, Bacterial / blood
            • Bacterial Outer Membrane Proteins / genetics
            • Bacterial Outer Membrane Proteins / metabolism
            • Disease Models, Animal
            • Ehrlichiosis / immunology
            • Ehrlichiosis / microbiology
            • Ehrlichiosis / physiopathology
            • HL-60 Cells
            • Horse Diseases / immunology
            • Horse Diseases / microbiology
            • Horse Diseases / physiopathology
            • Horses
            • Humans
            • Mice
            • Mice, Inbred C57BL
            • Reverse Transcriptase Polymerase Chain Reaction
            • Serial Passage
            • Transcription, Genetic

            Grant Funding

            • R01 AI041213 / NIAID NIH HHS
            • R01AI41213 / NIAID NIH HHS

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            Citations

            This article has been cited 11 times.
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