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Anaplasma phagocytophilum dihydrolipoamide dehydrogenase 1 affects host-derived immunopathology during microbial

Gang Chen1, Maiara S Severo, Olivia S Sakhon

  • 1Department of Entomology and Center for Disease Vector Research, University of California-Riverside, Riverside, California, USA.

Infection and Immunity
|July 4, 2012
PubMed

Insights

Anaplasma phagocytophilum lacking the lpda1 gene causes spleen enlargement and altered inflammation. This immunopathology is linked to reactive oxygen species and NF-κB signaling in macrophages, not neutrophils.

Area of Science:

  • Microbiology
  • Immunology
  • Pathogen Biology

Background:

  • Anaplasma phagocytophilum causes human granulocytic anaplasmosis, an inflammatory disease driven by host immune response rather than pathogen load.
  • Understanding Anaplasma phagocytophilum genes influencing inflammation is crucial for elucidating disease mechanisms.

Purpose of the Study:

  • To identify Anaplasma phagocytophilum genes affecting host inflammatory responses during infection.
  • To investigate the role of dihydrolipoamide dehydrogenase 1 (lpda1) in Anaplasma phagocytophilum-induced immunopathology.

Main Methods:

  • Utilized a Himar1 transposon mutant library of Anaplasma phagocytophilum to screen for genes affecting inflammation.
  • Analyzed clinicopathological abnormalities, spleen morphology, and extramedullary hematopoiesis in infected mammals.
  • Assessed reactive oxygen species production and nuclear factor-kappa B (NF-κB) signaling pathways in macrophages and neutrophils.

Main Results:

  • A transposon insertion in the lpda1 gene (APH_0065) significantly altered inflammation during infection.
  • Anaplasma phagocytophilum lacking lpda1 exhibited spleen enlargement, increased splenic extramedullary hematopoiesis, and other clinicopathological changes.
  • LPDA1-mediated immunopathology was independent of neutrophil infection and associated with increased reactive oxygen species and NF-κB activation in macrophages.

Conclusions:

  • The Anaplasma phagocytophilum lpda1 gene plays a critical role in modulating host inflammatory responses and disease pathogenesis.
  • Distinct signaling pathways are activated in neutrophils and macrophages during Anaplasma phagocytophilum infection.
  • LPDA1 is identified as a key immunopathological molecule in Anaplasma phagocytophilum infections.

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