title: Mycobacterium bovis BCG-infected neutrophils and dendritic cells cooperate to induce specific T cell responses in humans and mice.
abstract: Neutrophils are increasingly thought to modulate dendritic cell (DC) functions. We investigated the role of the neutrophil-DC partnership in the response to Mycobacterium bovis BCG-the vaccine used against tuberculosis. We compared neutrophil-DC crosstalk in humans and mice, searching for functional differences. In both species, neutrophils captured fluorescent BCG-enhanced green fluorescent protein (EGFP) and were more phagocytic than DC. Non-apoptotic BCG-infected neutrophils clustered with immature DC, establishing intimate contacts with dendrites, at which fluorescent intact bacilli were observed. Physical interactions between neutrophils and DC were required for DC activation. Human BCG-infected DC produced interleukin (IL)-10, an inhibitory cytokine, whereas DC exposed to BCG-infected neutrophils produced low to undetectable amounts of the cytokine. Mouse BCG-infected neutrophils induced sustained IL-2 production by DC. Human DC exposed to BCG-infected neutrophils stimulated recall T cell reactivity from vaccinated donors. Mouse DC infected with recombinant ovalbumin (OVA)-producing BCG (rBCG(ova)) elicited proliferation of TCR-OVA-transgenic CD4 and CD8 T cells. Moreover, exposing DC to rBCG(ova)-infected neutrophils enhanced OVA presentation. Thus, in mice and humans, neutrophils help DC to cross-present BCG antigens to T cells. Our results suggest that this "ménage à trois" involving neutrophils, DC and T cells plays a major role in the immune response to BCG.
authors.affiliation: Unité Mixte de Recherche 7151 CNRS, Université Paris 7, Laboratoire d'immunologie cellulaire et immunopathologie de l'Ecole Pratique des Hautes Etudes, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Morel
authors.forename: Edgar
authors.initials: E
authors.lastname: Badell
authors.forename: Valérie
authors.initials: V
authors.lastname: Abadie
authors.forename: Macarena
authors.initials: M
authors.lastname: Robledo
authors.forename: Niclas
authors.initials: N
authors.lastname: Setterblad
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Gluckman
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.forename: Sarah
authors.initials: S
authors.lastname: Boudaly
authors.forename: Nathalie
authors.initials: N
authors.lastname: Winter
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D006825:Hybridomas; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009163:Mycobacterium bovis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines