title: Moraxella catarrhalis adhesin UspA1-derived recombinant fragment rD-7 induces monocyte differentiation to CD14+CD206+ phenotype.
abstract: Circulating monocytes in the bloodstream typically migrate to other tissues and differentiate into tissue resident macrophages, the process being determined by the constituents of the microenvironments encountered. These may include microbes and their products. In this study, we investigated whether Moraxella catarrhalis Ubiquitous Surface Protein A1 (UspA1), known to bind to a widely expressed human cell surface receptor CEACAM1, influences monocyte differentiation as receptor engagement has been shown to have profound effects on monocytes. We used the recombinant molecules corresponding to the regions of UspA1 which either bind (rD-7; UspA1527-665) or do not bind (r6-8; UspA1659-863) to CEACAM1 and investigated their effects on CD206, CD80 and CD86 expression on freshly isolated human CD14+ monocytes from peripheral blood mononuclear cells (PBMC). Exposure to rD-7, but not r6-8, biased monocyte differentiation towards a CD14+CD206+ phenotype, with reduced CD80 expression. Monocytes treated with rD-7 also secreted high levels of IL-1ra and chemokine IL-8 but not IL-10 or IL-12p70. The effects of rD-7 were independent of any residual endotoxin. Unexpectedly, these effects of rD-7 were also independent of its ability to bind to CEACAM1, as monocyte pre-treatment with the anti-CEACAM antibody A0115 known to inhibit rD-7 binding to the receptor, did not affect rD-7-driven differentiation. Further, another control protein rD-7/D (a mutant form of rD-7, known not to bind to CEACAMs), also behaved as the parent molecule. Our data suggest that specific regions of M. catarrhalis adhesin UspA1 may modulate inflammation during infection through a yet unknown receptor on monocytes.
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xie
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Louise S
authors.initials: LS
authors.lastname: Brackenbury
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Darryl J
authors.initials: DJ
authors.lastname: Hill
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Williams
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong, P.R. China.
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Mumtaz
authors.initials: M
authors.lastname: Virji
mesh_terms: D000907:Antibodies, Bacterial / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D018925:Chemokines / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D001936:Moraxella catarrhalis / Q000378:metabolism*; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D015203:Reproducibility of Results
chemical_list: D000907:Antibodies, Bacterial; D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D018925:Chemokines; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C089675:UspA protein, Moraxella catarrhalis