title: Emergence, origin, and function of neutrophil-dendritic cell hybrids in experimentally induced inflammatory lesions in mice.
abstract: Although unusual neutrophils expressing major histocompatibility complex class II (MHC II) and costimulatory molecules have been detected at inflammatory sites in mice and humans, their identity, origin, and function remain unclear. We have demonstrated that, when cultured with granulocyte macrophage-colony-stimulating factor, neutrophils can give rise to a unique hybrid population exhibiting dual phenotypic and functionality of neutrophils and dendritic cells (DCs). Here we report that hybrid cells expressing surface markers of neutrophils (Ly6G, L-selectin, CXC chemokines receptor 2, and 7/4) and DCs (CD11c, MHC II, CD80, and CD86) become detectable in the peritoneal cavity, skin, lung, and lymph nodes under inflammatory conditions. Importantly, 20% to 30% of the adoptively transferred neutrophils acquired CD11c and MHC II expression when recovered from inflammatory lesions, demonstrating neutrophil → hybrid conversion in living animals. Using Escherichia coli strains expressing green fluorescent protein and ovalbumin, we further show hybrids play dual protective roles by rapidly clearing bacteria and presenting bacterial antigens to CD4 T cells. These results indicate that some of the neutrophils recruited to inflammatory lesions can differentiate into neutrophil-DC hybrids, thus challenging the classic view of neutrophils as terminally differentiated leukocytes destined to die or to participate primarily in host innate immunity.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Geng
authors.forename: Hironori
authors.initials: H
authors.lastname: Matsushima
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamoto
authors.forename: Yi
authors.initials: Y
authors.lastname: Yao
authors.forename: Ran
authors.initials: R
authors.lastname: Lu
authors.forename: Kristen
authors.initials: K
authors.lastname: Page
authors.forename: Robert M
authors.initials: RM
authors.lastname: Blumenthal
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Ward
authors.forename: Toru
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Akira
authors.initials: A
authors.lastname: Takashima
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000382:microbiology / Q000502:physiology*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006822:Hybrid Cells / Q000166:cytology / Q000382:microbiology / Q000502:physiology*; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000382:microbiology / Q000502:physiology*; D010538:Peritonitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins