Glucuronoxylomannan, a microbial compound, regulates expression of costimulatory molecules and production of cytokines in macrophages.
Glucuronoxylomannan (GXM) is a microbial compound that can modulate the immune response. We investigated (1) the receptors involved in uptake of GXM on monocyte-derived macrophages (MDMs) from healthy donors, (2) the effects of GXM on expression of specific receptors, (3) the effects of GXM mediated by pattern-recognition receptors, and (4) GXM modulation of MDM accessory and secretory functions. Cellular receptors involved in uptake of GXM included Fc gamma RII, CD18, Toll-like receptor (TLR) 4, and CD14. Some biological functions of MDMs were profoundly affected by treatment with GXM, resulting in (1) increased expression of CD40 and CD86 via perturbation of TLR4, (2) decreased expression of major histocompatibility complex class II, (3) induction of interleukin-10 but not of tumor necrosis factor-alpha, and (4) decreased lipopolysaccharide (LPS)-induced production of cytokines. GXM represents an attractive compound to limit inflammatory processes and induce an LPS-tolerant state.
Monari
Claudia
C
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia 06112, Italy.
Bistoni
Francesco
F
Casadevall
Arturo
A
Pericolini
Eva
E
Pietrella
Donatella
D
Kozel
Thomas R
TR
Vecchiarelli
Anna
A
D015703:Antigens, CD / Q000032:analysis*; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D020672:I-kappa B Proteins / Q000032:analysis; D007155:Immunologic Factors / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000032:analysis; D011134:Polysaccharides / Q000276:immunology* / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000032:analysis; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D020672:I-kappa B Proteins; D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C027478:glucuronoxylomannan