Emergence, origin, and function of neutrophil–dendritic cell hybrids in experimentally induced inflammatory lesions in mice

• Published in: Blood Vol. 121; no. 10; pp. 1690 - 1700
• Main Authors: Geng, Shuo, Matsushima, Hironori, Okamoto, Takashi, Yao, Yi, Lu, Ran, Page, Kristen, Blumenthal, Robert M., Ward, Nicole L., Miyazaki, Toru, Takashima, Akira
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.03.2013; American Society of Hematology
• Subjects: Animals; Antigen Presentation; Antigen-Presenting Cells - immunology; Biomarkers - metabolism; Blotting, Western; Cell Differentiation; Cells, Cultured; Cytokines - immunology; Cytokines - metabolism; Dendritic Cells - cytology; Dendritic Cells - microbiology; Dendritic Cells - physiology; Disease Models, Animal; Escherichia coli - pathogenicity; Escherichia coli Infections - immunology; Escherichia coli Infections - microbiology; Escherichia coli Infections - pathology; Flow Cytometry; Green Fluorescent Proteins - metabolism; Histocompatibility Antigens Class II - metabolism; Hybrid Cells - cytology; Hybrid Cells - microbiology; Hybrid Cells - physiology; Immunophenotyping; Inflammation - immunology; Inflammation - microbiology; Inflammation - pathology; Lung - immunology; Lung - microbiology; Lung - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils - cytology; Neutrophils - microbiology; Neutrophils - physiology; Peritonitis - etiology; Peritonitis - metabolism; Peritonitis - pathology; Plenary Paper; Skin - immunology; Skin - microbiology; Skin - pathology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2012-07-445197

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. •Neutrophils differentiate into neutrophil–dendritic cell hybrids upon recruitment to sites of inflammation or infection.•Hybrids play dual protective roles against bacterial infection by rapidly clearing bacteria and presenting bacterial antigens to T cells.