Effects of Anaplasma phagocytophilum on host cell ferritin mRNA and protein levels.
Ferritin is a major intracellular iron storage protein and also functions as a cytoprotectant by sequestering iron to minimize the formation of reactive oxygen species. Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis, is an obligate intracellular bacterium that colonizes neutrophils. We have previously reported that human promyelocytic HL-60 cells infected with A. phagocytophilum demonstrate increased transcription of ferritin heavy chain and also that the bacterium stimulates neutrophil NADPH oxidase assembly and degranulation during the initial hours of infection (J. A. Carlyon, W. T. Chan, J. Galan, D. Roos, and E. Fikrig, J. Immunol. 169:7009-7018, 2002, and J. A. Carlyon, D. Abdel-Latif, M. Pypaert, P. Lacy, and E. Fikrig, Infect. Immun. 72:4772-4783, 2004). In this study, we assessed ferritin mRNA and protein levels during A. phagocytophilum infection in vitro using HL-60 cells and neutrophils and in vivo using neutrophils from infected mice. The addition of A. phagocytophilum, as well as Escherichia coli and serum-opsonized zymosan, to neutrophils results in a pronounced increase in ferritin light-chain transcription and a concomitant rise in ferritin protein levels. Neutrophils from A. phagocytophilum-infected mice demonstrate elevated ferritin heavy-chain mRNA expression, a phenomenon consistent with infections by intracellular pathogens. Notably, ferritin protein levels of infected HL-60 cells were markedly diminished in a dose- and time-dependent manner. These studies provide insight into the effects A. phagocytophilum has on the ferritin levels of its host cell.
Carlyon
Jason A
JA
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Chandler Medical Center, 800 Rose Street, Room MN458A, Lexington, KY 40536-0298, USA. jason.carlyon@uky.edu
Ryan
Dara
D
Archer
Kristina
K
Fikrig
Erol
E
D041081:Anaplasma phagocytophilum / Q000502:physiology*; D000818:Animals; D016873:Ehrlichiosis / Q000382:microbiology; D005293:Ferritins / Q000096:biosynthesis* / Q000235:genetics*; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D009504:Neutrophils / Q000382:microbiology; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors
D021122:Protein Subunits; D012333:RNA, Messenger; D005293:Ferritins