PMID- 19570831
OWN - NLM
STAT- MEDLINE
DCOM- 20090806
LR  - 20090721
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 183
IP  - 3
DP  - 2009 Aug 1
TI  - Pneumococcal interaction with human dendritic cells: phagocytosis, survival, and 
      induced adaptive immune response are manipulated by PavA.
PG  - 1952-63
LID - 10.4049/jimmunol.0804383 [doi]
AB  - Dendritic cells (DCs) ingest and process bacteria for presenting their Ags to T 
      cells. PavA (pneumococcal adherence and virulence factor A) is a key virulence 
      determinant of pneumococci under in vivo conditions and was shown to modulate 
      adherence of pneumococci to a variety of nonprofessional phagocytic host cells. 
      Here, we demonstrated the role of PavA for the interaction of human DCs with live 
      pneumococci and analyzed the induced host cell responses upon ingestion of viable 
      pneumococci. Expression of PavA protected pneumococci against recognition and 
      actin cytoskeleton-dependent phagocytosis by DCs compared with isogenic pavA 
      mutants. A major proportion of internalized pneumococci were found in 
      membrane-bound phagosomes. Pneumococcal phagocytosis promotes maturation of DCs, 
      and both wild-type pneumococci and PavA-deficient pneumococci triggered 
      production of proinflammatory cytokines such as IL-1beta, IL-6, IL-8, IL-12, and 
      TNF-alpha and antiinflammatory IL-10. However, cytokine production was delayed 
      and reduced when DCs encounter pneumococci lacking PavA, which also results in a 
      less efficient activation of the adaptive immune response. Strikingly, purified 
      PavA reassociates to pneumococci but not DCs and reduced phagocytosis of the pavA 
      mutant to levels similar to those of wild-type pneumococci. Additionally, pavA 
      mutants covered with exogenously provided PavA protein induced a DC cytokine 
      profile similar to wild-type pneumococci. In conclusion, these results suggest 
      that PavA is key factor for live pneumococci to escape phagocytosis and to induce 
      optimal cytokine productions by DCs and adaptive immune responses as well.
FAU - Noske, Nadja
AU  - Noske N
AD  - Department Genetics of Microorganisms, Institute for Genetics and Functional 
      Genomics, University of Greifswald, Greifswald, Germany.
FAU - Kammerer, Ulrike
AU  - Kammerer U
FAU - Rohde, Manfred
AU  - Rohde M
FAU - Hammerschmidt, Sven
AU  - Hammerschmidt S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090701
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Bacterial Proteins)
RN  - 0 (Cytokines)
RN  - 0 (PavA protein, Streptococcus pneumoniae)
SB  - IM
MH  - Bacterial Proteins/genetics/*physiology
MH  - Cell Adhesion
MH  - Cell Survival/immunology
MH  - Cells, Cultured
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/*microbiology
MH  - Humans
MH  - *Immunity
MH  - Mutation
MH  - Phagocytosis/*immunology
MH  - Phagosomes/microbiology
MH  - Streptococcus pneumoniae/*pathogenicity
EDAT- 2009/07/03 09:00
MHDA- 2009/08/07 09:00
CRDT- 2009/07/03 09:00
PHST- 2009/07/03 09:00 [entrez]
PHST- 2009/07/03 09:00 [pubmed]
PHST- 2009/08/07 09:00 [medline]
AID - jimmunol.0804383 [pii]
AID - 10.4049/jimmunol.0804383 [doi]
PST - ppublish
SO  - J Immunol. 2009 Aug 1;183(3):1952-63. doi: 10.4049/jimmunol.0804383. Epub 2009 
      Jul 1.