PMID- 19047644
OWN - NLM
STAT- MEDLINE
DCOM- 20090130
LR  - 20240505
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 105
IP  - 49
DP  - 2008 Dec 9
TI  - S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic 
      cell and T cell functions.
PG  - 19474-9
LID - 10.1073/pnas.0810305105 [doi]
AB  - Dendritic cells (DCs) are antigen-presenting cells that play an essential role in 
      mucosal tolerance. They regularly encounter beneficial intestinal bacteria, but 
      the nature of these cellular contacts and the immune responses elicited by the 
      bacteria are not entirely elucidated. Here, we examined the interactions of 
      Lactobacillus acidophilus NCFM and its cell surface compounds with DCs. L. 
      acidophilus NCFM attached to DCs and induced a concentration-dependent production 
      of IL-10, and low IL-12p70. We further demonstrated that the bacterium binds to 
      DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a DC- specific receptor. To 
      identify the DC-SIGN ligand present on the bacterium, we took advantage of a 
      generated array of L. acidophilus NCFM mutants. A knockout mutant of L. 
      acidophilus NCFM lacking the surface (S) layer A protein (SlpA) was significantly 
      reduced in binding to DC-SIGN. This mutant incurred a chromosomal inversion 
      leading to dominant expression of a second S layer protein, SlpB. In the 
      SlpB-dominant strain, the nature of the interaction of this bacterium with DCs 
      changed dramatically. Higher concentrations of proinflammatory cytokines such as 
      IL-12p70, TNFalpha, and IL-1beta were produced by DCs interacting with the 
      SlpB-dominant strain compared with the parent NCFM strain. Unlike the 
      SlpA-knockout mutant, T cells primed with L. acidophilus NCFM stimulated DCs 
      produced more IL-4. The SlpA-DC-SIGN interaction was further confirmed as 
      purified SlpA protein ligated directly to the DC-SIGN. In conclusion, the major S 
      layer protein, SlpA, of L. acidophilus NCFM is the first probiotic bacterial 
      DC-SIGN ligand identified that is functionally involved in the modulation of DCs 
      and T cells functions.
FAU - Konstantinov, Sergey R
AU  - Konstantinov SR
AD  - Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB, 
      Wageningen, The Netherlands.
FAU - Smidt, Hauke
AU  - Smidt H
FAU - de Vos, Willem M
AU  - de Vos WM
FAU - Bruijns, Sven C M
AU  - Bruijns SC
FAU - Singh, Satwinder Kaur
AU  - Singh SK
FAU - Valence, Florence
AU  - Valence F
FAU - Molle, Daniel
AU  - Molle D
FAU - Lortal, Sylvie
AU  - Lortal S
FAU - Altermann, Eric
AU  - Altermann E
FAU - Klaenhammer, Todd R
AU  - Klaenhammer TR
FAU - van Kooyk, Yvette
AU  - van Kooyk Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081201
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Bacterial Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (S-layer proteins)
RN  - 0 (TLR2 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (surface layer protein A, Bacteria)
SB  - IM
MH  - Bacterial Proteins/genetics/*immunology/metabolism
MH  - Cell Differentiation/immunology
MH  - Cell Line
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology/*microbiology
MH  - Immune Tolerance/immunology
MH  - Kidney/cytology
MH  - Lactobacillus acidophilus/genetics/*immunology/metabolism
MH  - Macrophages/immunology/microbiology
MH  - Membrane Glycoproteins/genetics/immunology/metabolism
MH  - Mutagenesis
MH  - Probiotics
MH  - T-Lymphocytes/*immunology/*microbiology
MH  - Toll-Like Receptor 2/genetics/metabolism
MH  - Toll-Like Receptor 4/genetics/metabolism
MH  - Transfection
PMC - PMC2592362
COIS- The authors declare no conflict of interest.
EDAT- 2008/12/03 09:00
MHDA- 2009/01/31 09:00
PMCR- 2008/12/01
CRDT- 2008/12/03 09:00
PHST- 2008/12/03 09:00 [pubmed]
PHST- 2009/01/31 09:00 [medline]
PHST- 2008/12/03 09:00 [entrez]
PHST- 2008/12/01 00:00 [pmc-release]
AID - 0810305105 [pii]
AID - 5787 [pii]
AID - 10.1073/pnas.0810305105 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19474-9. doi: 
      10.1073/pnas.0810305105. Epub 2008 Dec 1.