Early transcriptional response of human neutrophils to Anaplasma phagocytophilum infection.
Anaplasma phagocytophilum, an unusual obligate intracellular pathogen that persists within neutrophils, causes human anaplasmosis (previously known as human granulocytic ehrlichiosis). To study the effects of this pathogen on the transcriptional profile of its host cell, we performed a comprehensive DNA microarray analysis of the early (4-h) transcriptional response of human neutrophils to A. phagocytophilum infection. A. phagocytophilum infection resulted in the up- and down-regulation of 177 and 67 neutrophil genes, respectively. These data were verified by quantitative reverse transcription-PCR of selected genes. Notably, the up-regulation of many antiapoptotic genes, including the BCL2A1, BIRC3, and CFLAR genes, and the down-regulation of the proapoptotic TNFSF10 gene were observed. Genes involved in inflammation, innate immunity, cytoskeletal remodeling, and vesicular transport also exhibited differential expression. Vascular endothelial growth factor was also induced. These data suggest that A. phagocytophilum may alter selected host pathways in order to facilitate its survival within human neutrophils. To gain further insight into the bacterium's influence on host cell gene expression, this report presents a detailed comparative analysis of our data and other gene expression profiling studies of A. phagocytophilum-infected neutrophils and promyelocytic cell lines.
Sukumaran
Bindu
B
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, The Anlyan Center for Medical Research and Education, New Haven, CT 06520-8031, USA.
Carlyon
Jason A
JA
Cai
Ji-Lian
JL
Berliner
Nancy
N
Fikrig
Erol
E
D041081:Anaplasma phagocytophilum / Q000472:pathogenicity*; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D009504:Neutrophils / Q000378:metabolism* / Q000382:microbiology*; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic; D015854:Up-Regulation