Noncanonical dendritic cell differentiation and survival driven by a bacteremic pathogen

Brodie Miles, Elizabeth Scisci, Julio Carrion, Gregory J. Sabino, Caroline A. Genco, Christopher W. Cutler

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Maintenance of blood DC homeostasis is essential to preventing autoimmunity while controlling chronic infection. However, the ability of bacteremic pathogens to directly regulate blood DC homeostasis has not been defined. One such bacteremic pathogen, Porphyromo-nas gingivalis, is shown by our group to survive within mDCs under aerobic conditions and therein, metastasize from its oral mucosal niche. This is accompanied by expansion of the blood mDC pool in vivo, independently of canonical DC poietins. We presently know little of how this bacteremic pathogen causes blood DC expansion and the pathophysiological significance. This work shows that optimum differentiation of MoDCs from primary human monocytes, with or without GM-CSF/IL-4, is dependent on infection with P. gingivalis strains expressing the DC-SIGN ligand mfa-1. DC differentiation is lost when DC-SIGN is blocked with its ligand HIV gp120 or knocked out by siRNA gene silencing. Thus, we have identified a novel, noncanonical pathway of DC differentiation. We term these PDDCs and show that PDDCs are bona fide DCs, based on phenotype and phagocytic activity when immature and the ability to up-regulate accessory molecules and stimulate allo-CD4+ T cell proliferation when matured. The latter is dependent on the P. gingivalis strain used to initially "educate" PDDCs. Moreover, we show that P. gingiva-lis-infected, conventional MoDCs become resistant to apoptosis and inflammatory pyroptosis, as determined by levels of Annexin V and caspase-8, -3/7, and -1. Taken together, we provide new insights into how a relatively asymptomatic bacteremia may influence immune homeostasis and promote chronic inflammation.

Original languageEnglish (US)
Pages (from-to)281-289
Number of pages9
JournalJournal of Leukocyte Biology
Volume94
Issue number2
DOIs
StatePublished - Aug 1 2013

Fingerprint

Dendritic Cells
Cell Differentiation
Cell Survival
Homeostasis
HIV Envelope Protein gp120
Ligands
Caspase 8
Annexin A5
Gingiva
Gene Silencing
Granulocyte-Macrophage Colony-Stimulating Factor
Bacteremia
Infection
Autoimmunity
Caspase 3
Interleukin-4
Small Interfering RNA
Monocytes
Up-Regulation
Maintenance

Keywords

  • Apoptosis
  • Inflammation
  • Periodontal pathogen
  • Porphyromonas gingivalis
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Noncanonical dendritic cell differentiation and survival driven by a bacteremic pathogen. / Miles, Brodie; Scisci, Elizabeth; Carrion, Julio; Sabino, Gregory J.; Genco, Caroline A.; Cutler, Christopher W.

In: Journal of Leukocyte Biology, Vol. 94, No. 2, 01.08.2013, p. 281-289.

Research output: Contribution to journalArticle

Miles, Brodie ; Scisci, Elizabeth ; Carrion, Julio ; Sabino, Gregory J. ; Genco, Caroline A. ; Cutler, Christopher W. / Noncanonical dendritic cell differentiation and survival driven by a bacteremic pathogen. In: Journal of Leukocyte Biology. 2013 ; Vol. 94, No. 2. pp. 281-289.
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