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Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
Modulation of NB4 promyelocytic leukemic cell machinery by Anaplasma phagocytophilum
Joao H F Pedra1, Bindu Sukumaran, Jason A Carlyon
1Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, The Anlyan Center for Medical Research and Education, 300 Cedar St., Room 525A P.O. Box 208031, New Haven, CT 06520-8031, USA.
Abstract:
Anaplasma phagocytophilum is a gram-negative obligate intracellular bacterium that persists within neutrophils. We assessed the impact of A. phagocytophilum infection in NB4 promyelocytic leukemic cells using high-density oligoarray, two-dimensional differential gel electrophoresis and liquid chromatography-mass spectrometry. Our Affymetrix data revealed that A. phagocytophilum altered the expression of transcription factors, cell adhesion molecules, signal transduction genes, and proinflammatory cytokines. However, the expression of Toll-like receptors, MYD88, RNF36, IRF3, and TBK1 and inhibitors of the NF-kappaB gene was not altered. A. phagocytophilum infection also altered the apoptotic program of NB4 cells and resulted in increased transcription of antiapoptotic genes (MCL1 and BFL1). The transcription and translation of iron-metabolism genes (light polypeptide ferritin chain, transferrin, and the transferrin receptor) were significantly altered, suggesting a possible link between A. phagocytophilum infection and iron metabolism. Our study clearly demonstrates multifactorial effects of A. phagocytophilum infection on NB4 promyelocytic leukemic cell machinery.
Insights
Anaplasma phagocytophilum infection impacts NB4 leukemic cells by altering gene expression, including antiapoptotic and iron metabolism genes. This study reveals multifactorial effects on cellular machinery.
Area of Science:
- Microbiology
- Molecular Biology
- Cell Biology
Background:
- Anaplasma phagocytophilum is a gram-negative obligate intracellular bacterium.
- It primarily infects and persists within neutrophils.
Purpose of the Study:
- To assess the impact of A. phagocytophilum infection on NB4 promyelocytic leukemic cells.
- To investigate the molecular mechanisms underlying the host-pathogen interaction.
Main Methods:
- High-density oligoarray analysis
- Two-dimensional differential gel electrophoresis (2D-DIGE)
- Liquid chromatography-mass spectrometry (LC-MS)
Main Results:
- A. phagocytophilum infection altered the expression of transcription factors, cell adhesion molecules, signal transduction genes, and proinflammatory cytokines.
- The expression of antiapoptotic genes (MCL1, BFL1) increased, while iron-metabolism genes showed significant alterations.
- Key immune signaling molecules like Toll-like receptors and NF-kappaB pathway components remained unchanged.
Conclusions:
- A. phagocytophilum infection has multifactorial effects on NB4 leukemic cell machinery.
- The bacterium influences host cell apoptosis and iron metabolism.
- Further research may explore the link between A. phagocytophilum and iron metabolism in host cells.

