Anaplasma phagocytophilum-induced gene expression in both human neutrophils and HL-60 cells.
Anaplasma phagocytophilum (Ap), the etiologic agent of the tick-borne disease human granulocytic anaplasmosis, is an obligate intracellular pathogen unique in its ability to target and replicate within neutrophils. We define and compare the spectra of host gene expression in response to Ap infection of human neutrophils and of HL-60 cells using long (70-mer)-oligonucleotide array technology. In addition to apoptosis-related genes, genes involved in signaling pathways, transcriptional regulation, immune response, host defense, cell adhesion, and cytoskeleton were modulated in neutrophils infected with Ap. Ap infection affected the same pathways in HL-60 cells but transcriptional changes occurred more slowly and in a reduced spectrum of genes. Gene expression changes detected by microarray were confirmed for randomly selected genes by QRT-PCR and Western blot studies. These studies demonstrate for the first time that the ERK pathway is activated in Ap-infected neutrophils and also define multiple pathways that are activated during intracellular Ap infection, which together serve to prolong the cell survival that is needed to allow bacterial replication and survival in neutrophils, which otherwise would rapidly apoptose.
Lee
Hin C
HC
Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Kioi
Mitomu
M
Han
Jing
J
Puri
Raj K
RK
Goodman
Jesse L
JL
D041081:Anaplasma phagocytophilum / Q000502:physiology*; D016873:Ehrlichiosis / Q000235:genetics / Q000382:microbiology*; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology*; D020411:Oligonucleotide Array Sequence Analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases