PMID- 22880012
OWN - NLM
STAT- MEDLINE
DCOM- 20130110
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 8
DP  - 2012
TI  - Divergent effects of mycobacterial cell wall glycolipids on maturation and 
      function of human monocyte-derived dendritic cells.
PG  - e42515
LID - 10.1371/journal.pone.0042515 [doi]
LID - e42515
AB  - BACKGROUND: Mycobacterium tuberculosis (Mtb) is able to evade the immune defenses 
      and may persist for years, decades and even lifelong in the infected host. Mtb 
      cell wall components may contribute to such persistence by modulating several 
      pivotal types of immune cells. Dendritic cells (DCs) are the most potent 
      antigen-presenting cells and hence play a crucial role in the initial immune 
      response to infections by connecting the innate with the adaptive immune system. 
      PRINCIPAL FINDINGS: We investigated the effects of two of the major mycobacterial 
      cell wall-associated types of glycolipids, mannose-capped lipoarabinomannan 
      (ManLAM) and phosphatidylinositol mannosides (PIMs) purified from the Mtb strains 
      H37Rv and Mycobacterium bovis, on the maturation and cytokine profiles of 
      immature human monocyte-derived DCs. ManLAM from Mtb H37Rv stimulated the release 
      of pro-inflammatory cytokines TNF, IL-12, and IL-6 and expression of 
      co-stimulatory (CD80, CD86) and antigen-presenting molecules (MHC class II). 
      ManLAM from M. bovis also induced TNF, IL-12 and IL-6 but at significantly lower 
      levels. Importantly, while ManLAM was found to augment LPS-induced DC maturation 
      and pro-inflammatory cytokine production, addition of PIMs from both Mtb H37Rv 
      and M. bovis strongly reduced this stimulatory effect. CONCLUSIONS: These results 
      indicate that the mycobacterial cell wall contains macromolecules of glycolipid 
      nature which are able to induce strong and divergent effects on human DCs; i.e 
      while ManLAM is immune-stimulatory, PIMs act as powerful inhibitors of DC 
      cytokine responses. Thus PIMs may be important Mtb-associated virulence factors 
      contributing to the pathogenesis of tuberculosis disease. These findings may also 
      aid in the understanding of some earlier conflicting reports on the 
      immunomodulatory effects exerted by different ManLAM preparations.
FAU - Mazurek, Jolanta
AU  - Mazurek J
AD  - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Ignatowicz, Lech
AU  - Ignatowicz L
FAU - Kallenius, Gunilla
AU  - Kallenius G
FAU - Svenson, Stefan B
AU  - Svenson SB
FAU - Pawlowski, Andrzej
AU  - Pawlowski A
FAU - Hamasur, Beston
AU  - Hamasur B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120803
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Glycolipids)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopeptides)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Phosphatidylinositols)
RN  - 0 (TLR2 protein, human)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (lipoarabinomannan)
RN  - 0 (phosphatidylinositol mannoside)
SB  - IM
MH  - Biomarkers/metabolism
MH  - Cell Differentiation/*drug effects
MH  - Cell Wall/*chemistry
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/*cytology/drug effects/*metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Genes, Reporter
MH  - Glycolipids/*pharmacology
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Limulus Test
MH  - Lipopeptides/pharmacology
MH  - Lipopolysaccharides/chemistry/immunology/isolation & purification/pharmacology
MH  - Monocytes/*cytology/drug effects/metabolism
MH  - Mycobacterium/*chemistry
MH  - Mycobacterium bovis/metabolism
MH  - Mycobacterium tuberculosis/metabolism
MH  - Phosphatidylinositols/chemistry/immunology/isolation & purification/pharmacology
MH  - Toll-Like Receptor 2/metabolism
MH  - Toll-Like Receptor 4/metabolism
PMC - PMC3411746
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/08/11 06:00
MHDA- 2013/01/11 06:00
PMCR- 2012/08/03
CRDT- 2012/08/11 06:00
PHST- 2011/05/18 00:00 [received]
PHST- 2012/07/10 00:00 [accepted]
PHST- 2012/08/11 06:00 [entrez]
PHST- 2012/08/11 06:00 [pubmed]
PHST- 2013/01/11 06:00 [medline]
PHST- 2012/08/03 00:00 [pmc-release]
AID - PONE-D-11-08962 [pii]
AID - 10.1371/journal.pone.0042515 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(8):e42515. doi: 10.1371/journal.pone.0042515. Epub 2012 Aug 3.