Mycobacterium bovis BCG Cell Wall-Specific Differentially Expressed Genes Identified by Differential Display and cDNA Subtraction in Human Macrophages

Nasim A. Begum, Kazuo Ishii, Mitsue Kurita-Taniguchi, Masako Tanabe, Mika Kobayashi, Yasuhiro Moriwaki, Misako Matsumoto, Yasuo Fukumori, Ichiro Azuma, Kumao Toyoshima, Tsukasa Seya

Research output: Contribution to journalArticle

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Abstract

We have analyzed the gene expression profile of monocytes in response to a highly purified cell wall fraction of Mycobacterium bovis BCG, a clinically approved adjuvant known as BCG cell wall skeleton (BCG-CWS). It is composed of mycolic acid, arabinogalactan, and peptidoglycan and confers Toll-like receptor 2 (TLR2)- and TLR4-dependent signaling that induces monocytes to differentiate into antigen-presenting cells (APCs). Here we report differential gene expression analysis with BCG-CWS-stimulated versus nonstimulated monocytes. BCG-CWS exerted massive induction of genes regulated by TLR signaling. Marked gene regulatory characteristics in BCG-CWS-stimulated cells compared to lipopolysaccharide (LPS)-stimulated cells follow. (i) Spliced mRNAs encoding soluble forms of TREM-1 and TREM-2 (recently discovered inflammatory-signal-amplifying receptors) were regulated by BCG-CWS, resulting in their differential expression. (ii) The genes for zinc-iron transporter protein (ZIP)-like family proteins HKE-1 and LIV-1 were induced exclusively by BCG-CWS. (iii) Interleukin-23 (IL-23), rather than IL-12p70, was induced by BCG-CWS, while interferon-inducible genes were induced only by LPS. By Northern and reverse transcription-PCR analyses, we confirmed the differential expression of more than 30 BCG-CWS regulatory genes, and their expression was compared with that of LPS and other known TLR ligands. A battery of genes responded rapidly and for a short time to LPS but for a long time to BCG-CWS. Structural analysis of the identified novel or hypothetical proteins revealed that some are potential candidates as signaling mediators or transcriptional regulators. Hence, BCG-CWS may profoundly modulate APC responses in a way distinct from that of LPS, leading to possible advantages for its adjuvant-active therapeutic potential.

Original languageEnglish
Pages (from-to)937-948
Number of pages12
JournalInfection and Immunity
Volume72
Issue number2
DOIs
Publication statusPublished - 2004 Feb
Externally publishedYes

Fingerprint

Cell Wall Skeleton
Mycobacterium bovis
Cell Wall
Complementary DNA
Macrophages
Genes
Lipopolysaccharides
Monocytes
Antigen-Presenting Cells
Regulator Genes
Mycolic Acids
Interleukin-23
Gene Expression
Toll-Like Receptor 2
Proteins
Peptidoglycan
Transcriptome
Interferons
Reverse Transcription

ASJC Scopus subject areas

  • Immunology

Cite this

Mycobacterium bovis BCG Cell Wall-Specific Differentially Expressed Genes Identified by Differential Display and cDNA Subtraction in Human Macrophages. / Begum, Nasim A.; Ishii, Kazuo; Kurita-Taniguchi, Mitsue; Tanabe, Masako; Kobayashi, Mika; Moriwaki, Yasuhiro; Matsumoto, Misako; Fukumori, Yasuo; Azuma, Ichiro; Toyoshima, Kumao; Seya, Tsukasa.

In: Infection and Immunity, Vol. 72, No. 2, 02.2004, p. 937-948.

Research output: Contribution to journalArticle

Begum, NA, Ishii, K, Kurita-Taniguchi, M, Tanabe, M, Kobayashi, M, Moriwaki, Y, Matsumoto, M, Fukumori, Y, Azuma, I, Toyoshima, K & Seya, T 2004, 'Mycobacterium bovis BCG Cell Wall-Specific Differentially Expressed Genes Identified by Differential Display and cDNA Subtraction in Human Macrophages', Infection and Immunity, vol. 72, no. 2, pp. 937-948. https://doi.org/10.1128/IAI.72.2.937-948.2004
Begum, Nasim A. ; Ishii, Kazuo ; Kurita-Taniguchi, Mitsue ; Tanabe, Masako ; Kobayashi, Mika ; Moriwaki, Yasuhiro ; Matsumoto, Misako ; Fukumori, Yasuo ; Azuma, Ichiro ; Toyoshima, Kumao ; Seya, Tsukasa. / Mycobacterium bovis BCG Cell Wall-Specific Differentially Expressed Genes Identified by Differential Display and cDNA Subtraction in Human Macrophages. In: Infection and Immunity. 2004 ; Vol. 72, No. 2. pp. 937-948.
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