    .  TLR        
  


           ,     ,       :     TLR-S,         ,            .





    

 TLR        



  


 



  ,2017



ISBN978-5-4485-6021-7

     Ridero


 ,      : ,   ,   ,        .         ,   ,         .   -   ,     -  ,   . Ƞ               :     ,         .     :  ,    ,  .   --  . ,       .




   







  ,   ,   


       ,     .Role ofTriggering Receptor Expressed on Myeloid Cells inthe Activation ofInnate Immunity

The innate immune system plays akey role intriggering asystemic inflammatory response (SIR). The triggering receptor expressed on myeloid cells (TREM51), which is located on neutrophils and monocytes, is involved inSIR, byregulating the effector mechanisms ofinnate immunity. Hyperproduction ofproinflammatory cytokines is apathogenetic component ofthe hyperergic phase ofacute systemic inflammation. The simultaneous activation ofToll5like receptors and TREM51 increases the production ofcytokines manifold. This is compensatory and adaptive, however, resulting indamage toorgans and tissues during excessive production ofcytokines.

    :

AKT   (Activation ofAkt/protein kinaseB);

AQ1  Q1 (Activator proteinQ1);

CD   (Cluster ofdifferentiation);

DAP12 -    12 (DNAXQactivating protein ofmolecular mass 12kilodaltons);

GMQCSF -   (Granulocyte macrophage colonystimulating factor);

HMGBQ1    Q1 (Highmobility group protein BQ1);

ICAM    (InterQCellular Adhesion Molecule);

IFN ?  ? (Interferon?);

IL  (Interleukin);

IRAKQ4 ILQ1    (ILQ 1RQassociated kinasesQ4);

IRF3    Q-3(Interferon regulatory factor3);

ITAM      (immunoreceptor tyrosineQbased activation motif);

LPS  (Lipopolysacharide);

MyD88       (Myeloid differentiation primary response protein88);

NF-kB   (Nuclear factorkB);

PGE2 GE2;

PI3K   (phosphoinositideQ3 kinase);

PLQ? Q?;

PRR   ;

RIP1    1(ReceptorQinteracting protein1);

TIRQ  Toll QIL1   (toll Qinterleukin

1receptor);

TLR Toll Qlike  (TollQlike receptor);

TNF?    ? (Tumor necrosis factor alpha);

TRAF6       Q6 (TNFQreceptorQassociated factor6);

TREMQ1  ,    (riggering receptor expressed on myeloid cellsQ1);

TRIF TIRQ  ,  IFNQ? (TIR domainQcontaining adaptorQinducing IFNQ?);

ʠ    (MitogenQactivated protein kinase)

 II ࠖ    II  (Major Histocompatibility ComplexII);

à 

        ()    .

         ,        .          - .     (, , , ,   )     PAMPs (-   )     PRRs (-  ).

 PRRs    Toll- like  (TLR),       (, ,  ,  ,    ),       (/   ),  (-)         ().          ( , , ,  ,  .),     ,   ,   . Ƞ ,     :          .

 PAMPs :

MAMPs (-   ), -   (, , , ).       FLS2.       FLS2-   ,       -       ;

DAMPs (   )  ,       .       DAMPs: S100  (   :   , ,   ,     ,    , , ).          ,   S100     -   S100  .  , ECLIA-  -       ( , , ,  -  .)    (HSP):      ,     ,  ,    ,    ,    Hsp70,    .  ,  HSP      .

TLRs,    ,      .   TLRs           .      :  - N-    1925,   (   ). -  ,     ,    .      TIR ,      IL-1.

   TLRs   ,      - , ,  ;       - , , , .








      TLR    20162017.




TLR-1


TLR-1-  ,  -   -  :  .    TLR-2.   ;        .

     ,           ,   1, 2, 4,   TIRAP   4500  ().     109   ,   101 .     : 533         305.

        TLR-1,     ,       .    -   ,      -?   TLR1 rs3923647  ,  -?     .








IFN-y expression inM. bovisBCG stimulated cultured PBMCs.

 (), ,    () ,       .      ,      , ,     .      toll-  TLR-1,     .

206  239 ,     TLR-1TLR-2,      .    ,   ,   ,  TLR1/2.  tnf NF-    .

TLR1248N          .



     TLR-1, TLR-2TLR-6    (mCRC).     FOLFIRI   (  , -5 ) + .        (228297 ).      + TLR-1     FOLFIRI+   mCRC.








  TLR1 TLR6                .



   TLR-1TLR-6432  .  ,      . Ѡ  ,         ()     ( )  .

,   ()   TLR1 rs5743551 ,           ( = 0,03).

         ,  ,  TLR1 rs5743551       .

  ,    TLR1       .  TLR6         .













 , ,        ,             .    -  ,   ()   > 5%      504   . ,    y         ().   - ,     .         (TLR1rs4833095)  TLR1.   ()       0.52(95%   (0.290.90), =0,006).    -1?    ?        ,     ().

  TLR1         ,     .



      TLR-1  .

TLR-1/2    -           (). 93 ,   ( ,     )    .    (IgE)     60,  .

TLR1    Pam3CSK4-   -? -12     -  , .  ,   /Ѡ    ,      IgE   ,  .

   ,  TLR1      th1/?2-,    IgE. ,              .



     TLR          .

  ,    (     )           .     -  ,     ..     ,     .  -        1       (  ).

TLR1          (0.600 0,005,  = 0.0003);    TLR6 (0.208 0.0165,  = 0.0059), TLR10 (0.00019 0.00014,  = 0.6238).   0.995 TLR1, TLR6  0.883, 0.546 TLR10.       0.0924 TLR1 ( = 95.2%,  = 100%, + = 13.80, - = 0.91) 0.0215 TLR6 ( = 85.7%,  = 82.8%, + = 4.98, - = 0.83).

   , TLR1        .          - .

   ,         , ,  . ,        -  ,  ,   -.  ,    ,           .          -,  ,  ,   CD4 (+) -,     .   ,   toll-  (tlrs) -  - ,         . ,      ,         .     tlrs  ,                 /  .          tlrs     ,         .








       .  - -  (tlrs) (TLR1, 2, 4, 5)      tlrs (TLR9)   .        - (NF-) -  (MAPKs). -1 Map- ,  ,     C-.  ,   , NOD-   (NLRP)    -1.   ,     - th1 -, th17-,   - (Tregs),      .

. baumannii = ,  acinetobacter baumannii; . coli =  ; .   =   ;  H. influenzae =  ; . i =  ; . pneumophila =  pneumophila;   =  ;  P. aeruginosa =  ; . i = .








    

   tlrs (   - ), -1- - (-),    1(-1),              .

  (   - ),    1(-1),     ,     ,         () -KB / -  (MAPKs).

.  =  ; . i =  ; .   =   ;  H. influenzae =  ; . i =  ; . pneumophila =  pneumophila; . is =  ;   = ; . i = .

    () ,        -     ( tlrs)     ,         -1(-1) .        ,          .

Toll-  (110),      (MyD88),     3(-3) -  1(-1) +        11 .

   15        ,      610   .

     ,            .



,  TLR ,  - .

TLR-S      .    TLR-S        .




  .


   .

   ,     (https://www.litres.ru/nikita-aleksandrovich-krivushkin/nacionalnoe-rukovodstvo-po-immunologii-patofiziologiya-tlr-i-ee-vliyanie-na-mehanizmy-razvitiya-patogeneza-zabolevaniy-immunnoy-sistemy/)  .

      Visa, MasterCard, Maestro,    ,   ,     ,  PayPal, WebMoney, ., QIWI ,       .


