title: Human neutrophil-expressed CD28 interacts with macrophage B7 to induce phosphatidylinositol 3-kinase-dependent IFN-gamma secretion and restriction of Leishmania growth.
abstract: We previously showed that CD28 is expressed on human peripheral blood neutrophils and plays an important role in CXCR-1 expression and IL-8-induced neutrophil migration. In this work we demonstrate that Leishmania major infection of macrophages results in parasite dose-dependent IL-8 secretion in vitro and in IL-8-directed neutrophil migration, as blocked by both anti-IL-8 and anti-IL-8R Abs, toward the L. major-infected macrophages. In the neutrophil-macrophage cocultures, both CTLA4-Ig, a fusion protein that blocks CD28-CD80/CD86 interaction, and a neutralizing anti-IFN-gamma Ab inhibit the anti-leishmanial function of neutrophils, suggesting that the neutrophil-macrophage interaction via CD28-CD80/CD86 plays an important role in the IFN-gamma-dependent restriction of the parasite growth. Cross-linking of neutrophil-expressed CD28 by monoclonal anti-CD28 Ab or B7.1-Ig or B7.2-Ig results in phosphatidylinositol 3-kinase association with CD28 and in wortmannin-sensitive but cyclosporin A-resistant induction and secretion of IFN-gamma. Whereas the neutrophils secrete IFN-gamma with CD28 signal alone, the T cells do not secrete the cytokine in detectable amounts with the same signal. Thus, neutrophil-expressed CD28 modulates not only the granulocyte migration but also induction and secretion of IFN-gamma at the site of infection where it migrates from the circulation.
authors.affiliation: National Center for Cell Science, Ganeshkhind, India.
authors.forename: K
authors.initials: K
authors.lastname: Venuprasad
authors.forename: Pinaki P
authors.initials: PP
authors.lastname: Banerjee
authors.forename: Subhasis
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Satyan
authors.initials: S
authors.lastname: Sharma
authors.forename: Subrata
authors.initials: S
authors.lastname: Pal
authors.forename: P B
authors.initials: PB
authors.lastname: Parab
authors.forename: Debashis
authors.initials: D
authors.lastname: Mitra
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Saha
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018122:B7-1 Antigen / Q000502:physiology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000096:biosynthesis / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016572:Cyclosporine / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006131:Growth Inhibitors / Q000276:immunology* / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism / Q000502:physiology; D018320:Leishmania major / Q000254:growth & development* / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000502:physiology; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D016572:Cyclosporine; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D007371:Interferon-gamma; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077191:Wortmannin; C497964:CD86 protein, human