title: The Numerical Predominance and Large Transcriptome Differences of Neutrophils in Peripheral Blood Together Inevitably Account for a Reported Pulmonary Tuberculosis Signature.
abstract: Previous transcriptomic analysis revealed a 393-transcript signature (PTBsig), which is dominated by interferon inducible genes, in whole blood of pulmonary tuberculosis (PTB) patients. Comparisons with a limited set of interferon-driven genes among separated monocytes, CD4+ T cells, CD8+ T cells, and neutrophils indicated that the signature is due to changes in neutrophils, the overwhelmingly predominant cell type. By extending the analysis to the entire 393 transcripts of PTBsig and by switching the cell proportions between separated monocytes, CD4+ T cells, CD8+ T cells, and neutrophils, we create putative PTBsig for whole blood (pPTBsig) in which CD4+ or CD8+ T cells or monocytes predominated or in which the cell proportions were unchanged. These putative signatures are then compared to the actual reported PTBsig. We show that, because of their predominance in peripheral blood and their larger transcriptional responses, neutrophils were indeed almost exclusively responsible for PTBsig. We caution that the functional significance of changes in other cell types might escape notice in transcriptome analysis that is based upon whole blood.
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China; Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Kang
authors.identifier: 0000-0002-9840-7671
authors.initials: K
authors.lastname: Wu
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China; Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Ka-Wing
authors.identifier: 0000-0001-8356-5880
authors.initials: KW
authors.lastname: Wong
authors.affiliation: State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Wang-Long
authors.initials: WL
authors.lastname: Deng
authors.affiliation: Department of Pathology, Qiqihar Medical University, Qiqihar 161006, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29634, USA.
authors.forename: Jing
authors.identifier: 0000-0001-5454-5135
authors.initials: J
authors.lastname: Li
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China; Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Douglas B
authors.identifier: 0000-0003-2689-9627
authors.initials: DB
authors.lastname: Lowrie
authors.affiliation: Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China; Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Xiao-Yong
authors.identifier: 0000-0001-6654-3559
authors.initials: XY
authors.lastname: Fan