PMID- 23113614
OWN - NLM
STAT- MEDLINE
DCOM- 20130328
LR  - 20211021
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 138
IP  - 3
DP  - 2013 Mar
TI  - The phagocytic capacity and immunological potency of human dendritic cells is 
      improved by alpha2,6-sialic acid deficiency.
PG  - 235-45
LID - 10.1111/imm.12025 [doi]
AB  - Dendritic cells (DCs) play an essential role in immunity against bacteria by 
      phagocytosis and by eliciting adaptive immune responses. Previously, we 
      demonstrated that human monocyte-derived DCs (MDDCs) express a high content of 
      cell surface alpha2,6-sialylated glycans. However, the relative role of these 
      sialylated structures in phagocytosis of bacteria has not been reported. Here, we 
      show that treatment with a sialidase significantly improved the capacity of both 
      immature and mature MDDCs to phagocytose Escherichia coli. Desialylated MDDCs had 
      a significantly more mature phenotype, with higher expression of MHC molecules 
      and interleukin (IL)-12, tumour necrosis factor-alpha, IL-6 and IL-10 cytokines, and 
      nuclear factor-kappaB activation. T lymphocytes primed by desialylated MDDCs 
      expressed more interferon-gamma when compared with priming by sialylated MDDCs. 
      Improved phagocytosis required E. coli sialic acids, indicating a mechanism of 
      host-pathogen interaction dependent on sialic acid moieties. The DCs harvested 
      from mice deficient in the ST6Gal.1 sialyltransferase showed improved 
      phagocytosis capacity, demonstrating that the observed sialidase effect was a 
      result of the removal of alpha2,6-sialic acid. The phagocytosis of different 
      pathogenic E. coli isolates was also enhanced by sialidase, which suggests that 
      modifications on MDDC sialic acids may be considered in the development of 
      MDDC-based antibacterial therapies. Physiologically, our findings shed new light 
      on mechanisms that modulate the function of both immature and mature MDDCs, in 
      the context of host-bacteria interaction. Hence, with particular relevance to 
      DC-based therapies, the engineering of alpha2,6-sialic acid cell surface is a novel 
      possibility to fine tune DC phagocytosis and immunological potency.
CI  - (c) 2012 The Authors. Immunology (c) 2012 Blackwell Publishing Ltd.
FAU - Cabral, M Guadalupe
AU  - Cabral MG
AD  - CEDOC, Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisboa, 
      Portugal.
FAU - Silva, Zelia
AU  - Silva Z
FAU - Ligeiro, Dario
AU  - Ligeiro D
FAU - Seixas, Elsa
AU  - Seixas E
FAU - Crespo, Helio
AU  - Crespo H
FAU - Carrascal, Mylene A
AU  - Carrascal MA
FAU - Silva, Mariana
AU  - Silva M
FAU - Piteira, Ana R
AU  - Piteira AR
FAU - Paixao, Paulo
AU  - Paixao P
FAU - Lau, Joseph T
AU  - Lau JT
FAU - Videira, Paula A
AU  - Videira PA
LA  - eng
GR  - CA16056/CA/NCI NIH HHS/United States
GR  - P01 HL107146/HL/NHLBI NIH HHS/United States
GR  - P01HL107146/HL/NHLBI NIH HHS/United States
GR  - R01 AI056082/AI/NIAID NIH HHS/United States
GR  - R01AI38193/AI/NIAID NIH HHS/United States
GR  - P30 CA016056/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Cytoskeletal Proteins)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
RN  - GZP2782OP0 (N-Acetylneuraminic Acid)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cytoskeletal Proteins/metabolism
MH  - Dendritic Cells/*immunology/*metabolism
MH  - Escherichia coli/immunology
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - N-Acetylneuraminic Acid/*deficiency/metabolism
MH  - Phagocytosis/genetics/*immunology
MH  - rho GTP-Binding Proteins/metabolism
PMC - PMC3573277
EDAT- 2012/11/02 06:00
MHDA- 2013/03/30 06:00
PMCR- 2014/03/01
CRDT- 2012/11/02 06:00
PHST- 2012/05/10 00:00 [received]
PHST- 2012/10/17 00:00 [revised]
PHST- 2012/10/22 00:00 [accepted]
PHST- 2012/11/02 06:00 [entrez]
PHST- 2012/11/02 06:00 [pubmed]
PHST- 2013/03/30 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - 10.1111/imm.12025 [doi]
PST - ppublish
SO  - Immunology. 2013 Mar;138(3):235-45. doi: 10.1111/imm.12025.