PMID- 21270122
OWN - NLM
STAT- MEDLINE
DCOM- 20110601
LR  - 20220309
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 13
DP  - 2011 Apr 1
TI  - Deconstructing tick saliva: non-protein molecules with potent immunomodulatory 
      properties.
PG  - 10960-9
LID - 10.1074/jbc.M110.205047 [doi]
AB  - Dendritic cells (DCs) are powerful initiators of innate and adaptive immune 
      responses. Ticks are blood-sucking ectoparasite arthropods that suppress host 
      immunity by secreting immunomodulatory molecules in their saliva. Here, compounds 
      present in Rhipicephalus sanguineus tick saliva with immunomodulatory effects on 
      DC differentiation, cytokine production, and costimulatory molecule expression 
      were identified. R. sanguineus tick saliva inhibited IL-12p40 and TNF-alpha while 
      potentiating IL-10 cytokine production by bone marrow-derived DCs stimulated by 
      Toll-like receptor-2, -4, and -9 agonists. To identify the molecules responsible 
      for these effects, we fractionated the saliva through microcon filtration and 
      reversed-phase HPLC and tested each fraction for DC maturation. Fractions with 
      proven effects were analyzed by micro-HPLC tandem mass spectrometry or 
      competition ELISA. Thus, we identified for the first time in tick saliva the 
      purine nucleoside adenosine (concentration of  approximately 110 pmol/mul) as a potent 
      anti-inflammatory salivary inhibitor of DC cytokine production. We also found 
      prostaglandin E(2) (PGE(2)  approximately 100 nM) with comparable effects in modulating 
      cytokine production by DCs. Both Ado and PGE(2) inhibited cytokine production by 
      inducing cAMP-PKA signaling in DCs. Additionally, both Ado and PGE(2) were able 
      to inhibit expression of CD40 in mature DCs. Finally, flow cytometry analysis 
      revealed that PGE(2), but not Ado, is the differentiation inhibitor of bone 
      marrow-derived DCs. The presence of non-protein molecules adenosine and PGE(2) in 
      tick saliva indicates an important evolutionary mechanism used by ticks to 
      subvert host immune cells and allow them to successfully complete their blood 
      meal and life cycle.
FAU - Oliveira, Carlo Jose F
AU  - Oliveira CJ
AD  - Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, 
      University of Sao Paulo, Ribeirao Preto, SP, Brazil.
FAU - Sa-Nunes, Anderson
AU  - Sa-Nunes A
FAU - Francischetti, Ivo M B
AU  - Francischetti IM
FAU - Carregaro, Vanessa
AU  - Carregaro V
FAU - Anatriello, Elen
AU  - Anatriello E
FAU - Silva, Joao S
AU  - Silva JS
FAU - Santos, Isabel K F de Miranda
AU  - Santos IK
FAU - Ribeiro, Jose M C
AU  - Ribeiro JM
FAU - Ferreira, Beatriz R
AU  - Ferreira BR
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110126
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CD40 Antigens)
RN  - 0 (IL10 protein, mouse)
RN  - 0 (Immunologic Factors)
RN  - 0 (Interleukin-12 Subunit p40)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology/*immunology/metabolism
MH  - CD40 Antigens/biosynthesis/immunology
MH  - Cells, Cultured
MH  - Cyclic AMP-Dependent Protein Kinases/immunology/metabolism
MH  - Dendritic Cells/cytology/*immunology/metabolism
MH  - Dinoprostone/biosynthesis/immunology
MH  - Immunologic Factors/*chemistry/*pharmacology
MH  - Interleukin-10/biosynthesis/immunology
MH  - Interleukin-12 Subunit p40/biosynthesis/immunology
MH  - Male
MH  - Mice
MH  - Rhipicephalus sanguineus/*chemistry
MH  - Saliva/*chemistry
MH  - Signal Transduction/drug effects/immunology
MH  - Toll-Like Receptors/immunology/metabolism
MH  - Tumor Necrosis Factor-alpha/biosynthesis/immunology
PMC - PMC3064151
EDAT- 2011/01/29 06:00
MHDA- 2011/06/02 06:00
PMCR- 2012/04/01
CRDT- 2011/01/29 06:00
PHST- 2011/01/29 06:00 [entrez]
PHST- 2011/01/29 06:00 [pubmed]
PHST- 2011/06/02 06:00 [medline]
PHST- 2012/04/01 00:00 [pmc-release]
AID - S0021-9258(20)53718-6 [pii]
AID - M110.205047 [pii]
AID - 10.1074/jbc.M110.205047 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Apr 1;286(13):10960-9. doi: 10.1074/jbc.M110.205047. Epub 2011 
      Jan 26.