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

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

  1. Shuo Geng1,
  2. Hironori Matsushima1,
  3. Takashi Okamoto1,
  4. Yi Yao1,
  5. Ran Lu1,
  6. Kristen Page2,
  7. Robert M. Blumenthal1,
  8. Nicole L. Ward3,
  9. Toru Miyazaki4, and
  10. Akira Takashima1,*
  1. 1 Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, OH, United States;
  2. 2 Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States;
  3. 3 Department of Dermatology, Case Western Reserve University, Cleveland, OH, United States;
  4. 4 Div. of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, University of Tokyo, Tokyo, Japan
  1. * Corresponding author; email: akira.takashima{at}utoledo.edu

Key points

  • Neutrophils differentiate into neutrophil-dendritic cell (DC) hybrids upon recruitment to sites of inflammation or infection.

  • Hybrids play dual protective roles against bacterial infection by rapidly clearing bacteria and presenting bacterial antigen to T cells.

Abstract

Although unusual neutrophils expressing MHC class II and co-stimulatory molecules have been detected at inflammatory sites in human patients and mice, their identity, origin, and function remain unclear. We have recently demonstrated in mice that, when cultured with GM-CSF, both immature and mature neutrophils can give rise to a unique population termed "neutrophil-dendritic cell (DC) hybrids" exhibiting dual phenotypic and functionality of neutrophils and DCs. Here we report that hybrid cells expressing surface markers of neutrophils (Ly6G, CD62L, CXCR2, 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, 20-30% of the adoptively transferred neutrophils acquired CD11c and MHC II expression when recovered from inflammatory lesions, demonstrating neutrophil → hybrid conversion in living animals. Using GFP- and OVA-expressing E. coli strains, we further show that neutrophil-DC 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 in vivo, thus, challenging the classic view of neutrophils as terminally differentiated leukocytes destined to die or to participate primarily in host innate immunity.

  • Submitted July 24, 2012.
  • Accepted December 22, 2012.