Blood Journal
Leading the way in experimental and clinical research in hematology

Neutrophil differentiation into a unique hybrid population exhibiting dual phenotype and functionality of neutrophils and dendritic cells

  1. Hironori Matsushima1,
  2. Shuo Geng1,
  3. Ran Lu1,
  4. Takashi Okamoto1,
  5. Yi Yao1,
  6. Nobuyasu Mayuzumi1,
  7. Paul F. Kotol2,
  8. Benjamin J. Chojnacki1,
  9. Toru Miyazaki3,
  10. Richard L. Gallo2, and
  11. Akira Takashima1
  1. 1Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, OH;
  2. 2Division of Dermatology, Department of Medicine, University of California at San Diego and VA San Diego Health Care System, San Diego, CA; and
  3. 3Division of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, University of Tokyo, Tokyo, Japan

Key Points

  • Both immature and mature neutrophils differentiate into a previously unrecognized hybrid population when cultured with GM-CSF.

  • The resulting hybrids exhibit dual phenotype and functionality of both neutrophils and dendritic cells.


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.

  • Submitted July 20, 2012.
  • Accepted December 20, 2012.
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