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

Begum, Noorzahan; Ishii, Kazuo; Kurita-Taniguchi, Mitsue; Tanabe, Masako; Kobayashi, Mika; Moriwaki, Yuji; Matsumoto, Misako; Fukumori, Yasuo; Azuma, Ichiro; Toyoshima, Kumao; Seya, Tsukasa

doi:10.1128/iai.72.2.937-948.2004

Cited by 73 publications

(75 citation statements)

References 55 publications

(80 reference statements)

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“…The gene regulatory profile of the monoacylated MDP was similar to that of BCG-CWS (49). No liberation of IFN-inducible genes was noticed in either case (data not shown), suggesting no involvement of the TRIF/TICAM-1 pathway (29,31).…”

Section: Discussionmentioning

confidence: 58%

Dendritic Cell Maturation Induced by Muramyl Dipeptide (MDP) Derivatives: Monoacylated MDP Confers TLR2/TLR4 Activation

Uehori

Fukase

Akazawa

et al. 2005

The Journal of Immunology

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6-O-acyl-muramyldipeptides (MDP) with various lengths of fatty acid chains were examined for their dendritic cell (DC) maturation activity expressed through TLRs. Judging from anti-TLR mAb/inhibitor-blocking analysis, MDP derivatives with a single octanoyl or stearoyl fatty acid chain were found to activate TLR2 and TLR4 on human DCs, although intact and diacylated MDP expressed no ability to activate TLRs. Human DC activation profiles by the monoacylated MDP were essentially similar to those by Calmette-Guérin (BCG)-cell wall skeleton (CWS) and BCG-peptidoglycan (PGN) based on their ability to up-regulate costimulators, HLA-DR, β2-microglobulin, and allostimulatory MLR. Monoacylated MDP induced cytokines with similar profiles to BCG-CWS or -PGN, although their potency for induction of TNF-α, IL-12p40, and IL-6 was less than that of BCG-CWS or -PGN. The MDP derivatives initiated similar activation in normal mouse macrophages, but exhibited no effect on TLR2/4-deficient or MyD88-deficient mouse macrophages. Mutation of d-isoGln to l-isoGln in monoacylated MDP did not result in loss of the DC maturation activity, suggesting marginal participation of nucleotide-binding oligomerization domain 2, if any, in monoacyl MDP-dependent DC maturation. These results define the adjuvant activity of 6-O-acyl MDP compounds at the molecular level. They target TLR2/TLR4 and act through the MyD88-dependent pathway in DCs and macrophages. Hence, the unusual combined activation of TLR2 and TLR4 observed with Mycobacterium tuberculosis is in part reflected in the functional properties of monoacylated MDP compounds. These findings infer that the essential minimal requirement for TLR2/4-mediated adjuvancy of BCG lies within a modified MDP.

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Section: Discussionmentioning

confidence: 58%

Dendritic Cell Maturation Induced by Muramyl Dipeptide (MDP) Derivatives: Monoacylated MDP Confers TLR2/TLR4 Activation

Uehori

Fukase

Akazawa

et al. 2005

The Journal of Immunology

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“…Recently, a putative soluble variant of human TREM-2 lacking a transmembrane domain was reported (43). This protein could act as a soluble receptor for LOS and Opa on bacterial membranes if produced by cells in the local environment of gonococcal infection.…”

Section: Discussionmentioning

confidence: 99%

TREM-2 binds to lipooligosaccharides of Neisseria gonorrhoeae and is expressed on reproductive tract epithelial cells

et al. 2008

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Triggering receptor expressed on myeloid cells-2 (TREM-2) is an innate immune receptor that initiates cellular activation upon ligation. In this study, we examined the interaction of TREM-2 with Neisseria gonorrhoeae using murine TREM-2A as it has been reported to recognize bacterial ligands. Using a whole bacteria ELISA, TREM-2A bound to all 6 strains in variable degrees. Far western blots of gonococcal outer membranes revealed TREM-2A binding to lipooligosaccharide (LOS) and Opa protein with predominant binding to LOS. Binding of TREM-2A to LOS was confirmed by ELISA and surface plasmon resonance. O-deacylation of the lipid A significantly reduced binding. Flow cytometry and reporter cell assays showed that gonococci bound to TREM-2A-transfected cells and induced transmembrane signaling. In humans, TREM-2 was constitutively expressed by genitourinary and fallopian tube epithelial cells, both of which are primary targets of gonococcal invasion. Ligation of TREM-2 by LOS induced IL-6 production in HeLa cervical carcinoma cells. To our knowledge, this is the first report of the expression of human TREM-2 by cells deriving from a non-myeloid lineage. We conclude that gonococci can interact with TREM-2 receptors through binding to LOS and Opa protein and initiate cell signaling and cytokine production.

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“…Because administration of rTREM-1 consisting of the extracellular domain effectively blocked septic shock (5), sTREM-1 might represent a negative feedback regulator of the inflammatory response during endotoxemia. Although evidence exists that sTREM-1 is a splice variant of TREM-1, the precise cellular source of sTREM-1 has not been clarified (4,15). Because endotoxemia leads to an immediate drop in the number of circulating granulocytes (8) due to sequestration to organs such as the lungs (16), the possibility exists that primarily TREM-1 high cells are sequestered, whereas TREM-1 low cells are released from the bone marrow, raising the impression of down-regulated TREM-1 expression on circulating granulocytes.…”

Section: Resultsmentioning

confidence: 99%

Cutting Edge: Expression Patterns of Surface and Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Human Endotoxemia

Knapp¹,

Gibot²,

Vos³

et al. 2004

The Journal of Immunology

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Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified molecule involved in the amplification of inflammation. To determine the regulation of TREM-1, we studied TREM-1 expression and soluble TREM-1 plasma levels upon i.v. LPS challenge in healthy humans in vivo and in vitro. Granulocyte TREM-1 expression was high at baseline and immediately down-regulated upon LPS exposure along with an increase in soluble TREM-1. Monocytes displayed a gradual up-regulation of TREM-1 upon LPS in vivo and in vitro. In vitro studies extended these findings to highly purified lipoteichoic acid and Streptococcus pneumoniae. Nonbacterial TLR ligands such as polyinosine-polycytidylic acid and imidazoquinoline, as well as the TLR9 ligand CpG, did not impact TREM-1 expression. The LPS-induced alterations in TREM-1 surface expression were not a result of increased TNF-α or IL-10. Inhibitor studies disclosed a PI3K-dependent pathway in LPS-induced up-regulation of TREM-1 on monocytes, whereas MAPK played a limited role.

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

Cited by 73 publications

References 55 publications

Dendritic Cell Maturation Induced by Muramyl Dipeptide (MDP) Derivatives: Monoacylated MDP Confers TLR2/TLR4 Activation

Dendritic Cell Maturation Induced by Muramyl Dipeptide (MDP) Derivatives: Monoacylated MDP Confers TLR2/TLR4 Activation

TREM-2 binds to lipooligosaccharides of Neisseria gonorrhoeae and is expressed on reproductive tract epithelial cells

Cutting Edge: Expression Patterns of Surface and Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Human Endotoxemia

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