title: Neutrophil differentiation into a unique hybrid population exhibiting dual phenotype and functionality of neutrophils and dendritic cells.
abstract: Neutrophils have been reported to acquire surface expression of MHC class II and co-stimulatory molecules as well as T-cell stimulatory activities when cultured with selected cytokines. However, cellular identity of those unusual neutrophils showing antigen presenting cell (APC)-like features still remains elusive. Here we show that both immature and mature neutrophils purified from mouse bone marrow differentiate into a previously unrecognized "hybrid" population showing dual properties of both neutrophils and dendritic cells (DCs) when cultured with granulocyte macrophage-colony-stimulating factor but not with other tested growth factors. The resulting hybrid cells express markers of both neutrophils (Ly6G, CXCR2, and 7/4) and DCs (CD11c, MHC II, CD80, and CD86). They also exhibit several properties typically reserved for DCs, including dendritic morphology, probing motion, podosome formation, production of interleukin-12 and other cytokines, and presentation of various forms of foreign protein antigens to naïve CD4 T cells. Importantly, they retain intrinsic abilities of neutrophils to capture exogenous material, extrude neutrophil extracellular traps, and kill bacteria via cathelicidin production. Not only do our results reinforce the notion that neutrophils can acquire APC-like properties, they also unveil a unique differentiation pathway of neutrophils into neutrophil-DC hybrids that can participate in both innate and adaptive immune responses.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Hironori
authors.initials: H
authors.lastname: Matsushima
authors.forename: Shuo
authors.initials: S
authors.lastname: Geng
authors.forename: Ran
authors.initials: R
authors.lastname: Lu
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamoto
authors.forename: Yi
authors.initials: Y
authors.lastname: Yao
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Mayuzumi
authors.forename: Paul F
authors.initials: PF
authors.lastname: Kotol
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Chojnacki
authors.forename: Toru
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
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* / Q000502:physiology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006822:Hybrid Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis; D010641:Phenotype
chemical_list: D015415:Biomarkers; D016207:Cytokines