Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209+ dendritic cells for immune T cell areas

Cheolho Cheong, Ines Matos, Jae Hoon Choi, Durga Bhavani Dandamudi, Elina Shrestha, M. Paula Longhi, Kate L. Jeffrey, Robert M. Anthony, Courtney Kluger, Godwin Nchinda, Hyein Koh, Anthony Rodriguez, Juliana Idoyaga, Maggi Pack, Klara Velinzon, Chae Gyu Park, Ralph M. Steinman

Research output: Contribution to journalArticlepeer-review

448 Scopus citations

Abstract

Dendritic cells (DCs), critical antigen-presenting cells for immune control, normally derive from bone marrow precursors distinct from monocytes. It is not yet established if the large reservoir of monocytes can develop into cells with critical features of DCs in vivo. We now show that fully differentiated monocyte-derived DCs (Mo-DCs) develop in mice and DC-SIGN/CD209a marks the cells. Mo-DCs are recruited from blood monocytes into lymph nodes by lipopolysaccharide and live or dead gram-negative bacteria. Mobilization requires TLR4 and its CD14 coreceptor and Trif. When tested for antigen-presenting function, Mo-DCs are as active as classical DCs, including cross-presentation of proteins and live gram-negative bacteria on MHC I in vivo. Fully differentiated Mo-DCs acquire DC morphology and localize to T cell areas via L-selectin and CCR7. Thus the blood monocyte reservoir becomes the dominant presenting cell in response to select microbes, yielding DC-SIGN+ cells with critical functions of DCs.

Original languageEnglish (US)
Pages (from-to)416-429
Number of pages14
JournalCell
Volume143
Issue number3
DOIs
StatePublished - Oct 29 2010
Externally publishedYes

Keywords

  • Cellbio
  • Cellimmuno
  • Humdisease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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