title: Spontaneous or Mycobacterium tuberculosis-induced apoptotic neutrophils exert opposite effects on the dendritic cell-mediated immune response.
abstract: Polymorphonuclear neutrophils (PMN) modulate the adaptive immune response through interactions with immature dendritic cells (iDC) while spontaneous apoptotic neutrophils PMNapo (PMNapo) may have an inhibitory effect on DC functions. We investigate the effect exerted by PMNapo in DC maturation and the role of Mycobacterium tuberculosis (Mtb)-induced PMNapo in the cross-presentation of mycobacterial antigens. We demonstrate that Mtb triggers the maturation of iDC while it is impaired by the presence of PMNapo, which abrogate Mtb-induced expression of costimulatory and HLA class II molecules, reducing IL-12 and IFN-gamma release by DC and partially inhibiting Mtb-driven lymphocyte proliferation. This inhibitory effect is not observed in already Mtb-matured DC, and it involves a direct interaction between DC and PMNapo, as supernatants from PMNapo cultures do not reveal this effect. Although PMNapo do not alter Mtb/DC-SIGN interaction, they affect the intracellular signals leading to DC maturation without requiring their entry into DC. Phagocytosis of Mtb-induced PMNapo by iDC leads to lymphoproliferation, which is significantly reduced by blocking CD36 and not DC-SIGN on iDC. Therefore, cross-presentation of Mtb antigens is taking place. Our findings suggest that the inflammatory milieu is subjected to a fine balance between non-infected and Mtb-induced PMNapo: non-infected PMNapo limiting inflammation and Mtb-induced PMNapo generating a specific immune activity.
authors.affiliation: IIHema, Academia Nacional de Medicina, and Servicio de Tisioneumonología, Hospital Muñiz, Buenos Aires, Argentina. maleman@hematologia.anm.edu.ar
authors.forename: Mercedes
authors.initials: M
authors.lastname: Alemán
authors.forename: Silvia
authors.initials: S
authors.lastname: de la Barrera
authors.forename: Pablo
authors.initials: P
authors.lastname: Schierloh
authors.forename: Noemí
authors.initials: N
authors.lastname: Yokobori
authors.forename: Matías
authors.initials: M
authors.lastname: Baldini
authors.forename: Rosa
authors.initials: R
authors.lastname: Musella
authors.forename: Eduardo
authors.initials: E
authors.lastname: Abbate
authors.forename: María
authors.initials: M
authors.lastname: Sasiain
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D051940:B7-2 Antigen / Q000378:metabolism; D018955:CD36 Antigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D015638:Cytochalasin D / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007136:Immunoglobulins / Q000378:metabolism; D016023:Integrins / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007700:Kinetics; D037181:Lectins, C-Type / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D011725:Pyridines / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000097802:CD83 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051940:B7-2 Antigen; D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; D015638:Cytochalasin D; D004791:Enzyme Inhibitors; D006684:HLA-DR Antigens; D007093:Imidazoles; D007136:Immunoglobulins; D016023:Integrins; D007371:Interferon-gamma; D018664:Interleukin-12; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011725:Pyridines; D011956:Receptors, Cell Surface; D019030:Receptors, Vitronectin; D048051:p38 Mitogen-Activated Protein Kinases; D000097802:CD83 Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C497964:CD86 protein, human; C064660:integrin alphaVbeta5; C050016:lipoarabinomannan; C093642:SB 203580