Transcript Slide 1

tuberkuloziT daavadebisadmiGgenetikuri winaswarganwyobis aspeqtebi
Nnona TadumaZe
tuberkulozisa da filtvis daavadebaTa erovnuli centri
22 Tebervali 2011
Temis aqtualoba
• faqti, rom M.tuberculosis-iT inficirebis mxolod 5-10% Rebulobs aqtiuri daavadebis formas,
metyvelebs tuberkulozis ganviTarebaSi adamianis genomis individualuri variabelobis rolze
• antibiotikoTerapiis Tanamedrove krizisi
• axali samkurnalo strategiebis (maT Soris –
gaumjobesebis aucilebloba
imunointervenciaze damyarebuli) SemuSavebisa da
maspinZeli organizmis genomis funqciuri kvlevis mniSvneloba
• paTogenezis meqanizmebis ufro Rrma wvdoma
• axali, makroorganizmis resursebze dafuZnebuli, prevenciuli da Terapiuli RonisZiebebis
SemuSaveba da ganviTareba
• imunointervenciaze damyarebuli strategiebis ganviTareba
tuberkulozisadmi gansxvavebuli mgrZnobeloba Tagvis genetikur xazebSi
•
A/Sn – tuberkulozisadmi mdgradi xazi
•
I/St – tuberkulozisadmi maRalmgrZnobiare xazi (genomi - Slc11a1(r)):
inficirebis Sedegad daavadebis myisieri ganviTareba
mZime mimdinareoba
xSiri leTaluri gamosavali
makrofagebiT infiltracia
makrofaguli derivatebis maRali homogenizacia
filtvis qsovilSi neitrofilebis akumulacia
DdaavadebaTa klasifikacia
genetikuri da garemo faqtorebis
xvedriTi wilis mixedviT
I jgufi – qromosomuli sindromebi
II jgufi _ monogenuri daavadebebi
III jgufi _ multifaqtoruli (poligenuri) daavadebebi
IV jgufi _ minimaluri genetikuri komponentiT
K
koncefcia: geni →→ cila →→ funqcia
PAMP (Pathogen associated molecular Patterns) ↔ PRRs (Pattern
recognition Receptors)
• paTogenis mitaceba alveoluri makrofagebis (Mφ) mier (PRRs receptorebis gziT) da
fagocituri aqtivacia citokinebiT (IFN-γ)
•baqteriebis daSlis iniciacia reaqtiuli oqsigenuri intermediatoruli (ROI) da reaqtiuli nitrogenuli
intermediatoruli (RNI) faqtorebis saSualebiT, intrafagocituri NO-is produqcia
• dendruli ujredebis saSualebiT mikobaqteriis transporti filtvis mukozidan limfur kvanZebSi
• T -sistemis aqtivacia Mφ-is (antigen-asocirebuli sxva ujredebis) saSualebiT
• T-sistemis mier citokinebisa da qemokinebis aqtivacia
•qemokinebis mier damatebiTi fagocituri ujredebis mobilizacia infeqciis keraSi
•T-helperuli sistemis bipotenturiprekursorebi _ ThP stimulirdeba, romlebic, Tavis mxriv,
stimulireben Th citokinebs
• CD-mediatoruli hipersensitiuri reaqciis Sedegad tuberkulozuri granulomis Camoyalibeba
PRRs (Pattern Recognition Receptors) tipebi
I – membranuli faqtorebi:
• receptoruli kinazebi
• Toll-like receptorebi (TLRs)
• manozas receptorebi (MRs)
II – citoplazmuri faqtorebi:
• NOD-like receptorebi (NLRs)
• NOD-receptorebi (NODs)
• IL1-asocirebuli kinazebi (IRAKs)
TLR (Toll-like) receptorebi
funqcia: mikrobul agentebze
sapasuxod citokinebisa da
imunuri ujredebis aqtivacia
meqanizmi: signalis transduqcia
birTvul faqtorebad, romlebic
aqtivireben an inhibireben
pirvelad imunur reaqcias,
rac, Tavis mxriv, modificirebs
citokinebis realizacias
genetikuri cvalebadobis Sedegi:
kappa-B signalis transduqciisa
da intracitoplazmuli cilebis:
nukleotiduri oligomeruli
domenebisa (NOD) da kaspazas
sistemis blokireba, Sedegad _ imunuri reaqciis inhibireba da Sesabamisi
klinikuri efeqti
• Toll-like receptorebisa (TLR) da interleikin-1 receptorebis (IL-1R) sasignalo komponentebi:
adaptoruli cila _ MyD88
interaqtiuli cila _ TOLLIP
proteinkinaza _ IRAK (IL-1R asocirebuli kinaza)
TRAF6 (TNF-receptorTan asocirebuli cila)
• TRAF6 aqtivirebs birTvul B-faqtorebs:
(NF- B) kinaza TAK1-is saSualebiT.
agreTve – kinazebs: JNK da p38 MAP mitogeniT aqtivirebuli proteinkinazis saSualebiT
TLR evolucia
• evoluciurad uZvelesi
da maRalkonservatiuli
sistema
• ZuZumwovarTa saxeobebis
umravlesobaSi 10-15 tipis
• adamianSi 13 tipis
(TLRs1-TLRs13)
• saxeobrivi gansxvavebebi TLRs tipebis kombinaciebis mixedviT, rac winaaRmdegobas uqmnis cxovelebis,
rogorc adamianis imunogenetikis modelis, Seswavlas am mimarTulebiT
TLR genetikuri struqtura
TLR polimorfizmi
•
Genetic association and expression studies indicate a role of toll-like receptor 8 in
pulmonary tuberculosis. Davila S, Hibberd ML, Hari Dass R, Wong HE, Sahiratmadja E,
Bonnard C, Alisjahbana B, Szeszko JS, Balabanova Y, Drobniewski F, van Crevel R, van de
Vosse E, Nejentsev S, Ottenhoff TH, Seielstad M. PLoS Genet. 2008 Oct;4(10):e1000218.
Epub 2008 Oct 10
• gamovlinda, X-qromosomaze lokalizebuli, TLR8-genis arasinonimuri polimorfizmis _
rs3764880 (Met/Val) _ kavSiri tuberkulozis SemTxvevebTan mamakacebSi
• genis eqspresiis analizma aCvena, TLR8-transkriptis mniSvnelovani up-regulacia daavadebis mwvave
fazaSi
•
Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis
in Caucasians, African-Americans, and West Africans. Velez DR, Wejse C, Stryjewski ME,
Abbate E, Hulme WF, Myers JL, Estevan R, Patillo SG, Olesen R, Tacconelli A, Sirugo G,
Gilbert JR, Hamilton CD, Scott WK. Hum Genet. 2010 Jan;127(1):65-73. Epub 2009 Sep 22
• 474 individi afroamerikuli populaciidan
381 _ evropuli populaciidan
667 _ afrikuli populaciidan
• TLR1, TLR2, TLR4, TLR6, TLR9 71 saxis polimorfizmi
• aqtiuri tuberkulozis SemTxvevebis statistikurad sarwmuno korelacia TLR9 da TLR2
polimorfizmebTan
•
Association of TIRAP (MAL) gene polymorphisms with susceptibility to
tuberculosis in a Chinese population. Zhang YX, Xue Y, Liu JY, Zhao MY, Li FJ,
Zhou JM, Wang HJ, Li JC. Genet Mol Res. 2011 Jan 4;10(1):7-15
• tuberkuloziT daavadebuli 212 pacienti da 215 janmrTeli individi
• Toll-like-receptorebis signalis adaptoruli faqtoris _ Toll-interleikin-1 receptoruli domenis
(TIR) adaptoruli cilis _ATIRAP genis polimorfizmi
• 286AG genotipi mniSvnelovnad maRali iyo pacientebSi kontrolTan SedarebiT
•
Toll-like receptor and TIRAP gene polymorphisms in pulmonary tuberculosis patients of
South India. Selvaraj P, Harishankar M, Singh B, Jawahar MS, Banurekha VV. Tuberculosis
(Edinb). 2010 Sep;90(5):306-10. Epub 2010 Aug 24
•
polimorfizmebi:
TLR-1 1805T/G (Ile602Ser)
TLR-2 2258G/A (Arg753Gln)
TLR-4 896A/G (Asp299Gly)
TLR-4 1196C/T (Thr399Ile)
TLR-6 745C/T (Ser249Pro)
TIRAP 975C/T (Ser180Leu)
TLR-9 1237C/T., 1486C/T
•
RFLP genotipireba
•
filtvis tuberkuloziT daavadebuli 206 pacienti da 212 janmrTeli individi
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Toll-IL1-receptoruli domenis adaptoruli cilis TIRAP genis polimorfuli (Ser180Leu) genotipis sixSire
mniSvnelovnad maRalia tuberkuloziT daavadebuli pacientebis jgufSi
•
Toll-like receptor 2 gene polymorphisms, pulmonary tuberculosis, and natural
killer cell counts. Chen YC, Hsiao CC, Chen CJ, Chin CH, Liu SF, Wu CC, Eng HL,
Chao TY, Tsen CC, Wang YH, Lin MC. BMC Med Genet. 2010 Jan 30;11:17
• tuberkuloziT daavadebisadmi sensiturobis korelacia TLR2 haplotipTan _ [A-G-(Insertion)-T]
• plevritebiT mimdinare SemTxvevebSi, plevritebis gareSe mimdinare SemTxvevebTan SedarebiT, maRali
iyo 1350 CC genotipis sixSire
Aanionebis RviZlis satransporto sistema
•
Effects of tuberculosis, race, and human gene SLCO1B1 polymorphisms on rifampin concentrations.
Weiner M, Peloquin C, Burman W, Luo CC, Engle M, Prihoda TJ, Mac Kenzie WR, Bliven-Sizemore E,
Johnson JL, Vernon A. Antimicrob Agents Chemother. 2010 Oct;54(10):4192-200. Epub 2010 Jul 26
•
Association of SLC11A1 with tuberculosis and interactions with NOS2A and TLR2 in AfricanAmericans and Caucasians. Velez DR, Hulme WF, Myers JL, Stryjewski ME, Abbate E, Estevan
R, Patillo SG, Gilbert JR, Hamilton CD, Scott WK. Int J Tuberc Lung Dis. 2009 Sep;13(9):1068-76
•
Effect of drug transporter genotypes on pravastatin disposition in European- and African-American
participants. Ho RH, Choi L, Lee W, Mayo G, Schwarz UI, Tirona RG, Bailey DG, Michael Stein C, Kim
RB. Pharmacogenet Genomics. 2007 Aug;17(8):647-56
• anionebis RviZlis satrasporto sistemis SLCO1B1-genis polimorfizmis korelacia rifampicinis
farmakokinetikuri maCveneblebis individualur variabelobasTan
• genis polimorfuli varianti _ 463C>A _ ganapirobebda rifampicinis farmakologiuri moqmedebis
daqveiTebas
• 463C>A polimorfizmi da Sedegad, rifampicinis farmakologiuri zemoqmedebis SedarebiT dabali
maCvenebeli, upiratesad, aRiniSna Sav rasaSi
vitamini D _ tuberkulozuri infeqciis supresori
•
D vitaminis metabolitebis imunomodulatoruli aqtivobis samizne:
monocitebis aqtivaciis procesi
imunoglobulinebis produqciis procesi
citokinebis sekreciis procesi
•
1,25(OH)2D3 imunomodulatoruli potencia:
dendruli ujredebis ko-stimulatorebis eqspresiis regulacia
IL produqciis regulacia
Th2 ganviTarebis stimulacia
•
vitamin D-damokidebuli NO-produqciis stimulacia 1,25(OH)2D3 saSualebiT
•
1,25(OH)2D3 da D vitaminis receptorebis (VDR) saSualebiT adamianis antimikrobuli peptidebis eqspresiis regulacia
•
D vitaminuri metabolitebi axorcieleben imunuri sistemis rogorc up-regulacias monocitebisa da makrofagebis populaciebis
fagocitaruli ativaciis gziT, ise _ down-regulacias (MHC II inhibiciis gziT) SeZenili imunitetis farglebSi
•
Genetic polymorphisms in vitamin D receptor, vitamin D-binding protein, Toll-like receptor 2, nitric
oxide synthase 2, and interferon-gamma genes and its association with susceptibility to tuberculosis.
Leandro AC, Rocha MA, Cardoso CS, Bonecini-Almeida MG. Braz J Med Biol Res. 2009 Apr;42(4):31222
•
Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants
from sub-Saharan Africa. Gibney KB, MacGregor L, Leder K, Torresi J, Marshall C, Ebeling PR, et al
Clin Infect Dis 2008; 46: 443-446
•
Solar ultraviolet radiation and vitamin D: a historical perspective.Rajakumar K, Greenspan SL,
Thomas SB, Holick MF. Am J Public Health 2007; 97: 1746-1754
•
sisxlis plazmaSi D vitaminis dabali koncentacia korelirebs tuberkulozis momatebul riskTan
•
sisxlis plazmaSi D vitaminis maRali koncentracia korelirebs tuberkulozis nakleb SemTxvevebTan
•
•
•
Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D
receptor gene. Bellamy R, Ruwende C, Corrah T, McAdam KP, Thursz M, Whittle HC, et al. J Infect Dis
1999; 179: 721-724
Association of vitamin D receptor genotypes with the susceptibility to pulmonary tuberculosis in
female patients & resistance in female contacts. Selvaraj P, Narayanan PR, Reetha AM. Indian J Med
Res 2000; 111: 172-179
Association between vitamin D receptor gene polymorphisms and response to treatment of
pulmonary tuberculosis. Roth DE, Soto G, Arenas F, Bautista CT, Ortiz J, Rodriguez R, et al. J Infect Dis
2004; 190: 920-927
•
rogorc D vitaminis sinTezis variabeluroba, ise misi receptoruli genebis (VDR) polimorfizmi asocirebulia
tuberkulozisadmi winaswarganwyobasTan
•
VDR polimorfizmebi (12q12-14):
BB, Bb,bb (Bsm I)
AA, Aa, aa (Apa I)
TT, Tt, tt (Taq I)
•
tt genotipi (9 ekzoni) asocirebulia tuberkulozis dabal riskTan
•
peruSi genotipi Tt dakavSirebuli iyo TerapiisSemdgom swraf kulturalur konversiasTan
citokinebi
•
Interleukin-10 (IL-10) gene polymorphism as a potential host susceptibility factor
in tuberculosis. Oral HB, Budak F, Uzaslan EK, Baştürk B, Bekar A, Akalin H, Ege E,
Ener B, Göral G. Cytokine. 2006 Aug;35(3-4):143-7. Epub 2006 Sep 7
• dadgenilia IL-10 genis polimorfizmis korelacia tuberkuloziT daavadebis riskTan
• IL-10-1082G alelis sixSire mniSvnelovnad maRali iyo tuberkuloziT daavadebul pacientebSi
janmrTel kontrolTan SedarebiT
• niSnis mixedviT statistikurad sarwmuno gansxvaveba ar iqna dafiqsirebuli daavadebis sxvadasxva klinikur
formebs Soris
gama-interferoni
• gama-interferonis interaqtiuli funqcia araspecifikuri da specifikuri imunur sistemebs Soris
• genis polimorfizmi A/T 874 poziciaSi kavSirSia tuberkulozis riskTan
• genebi:
IFN- γ - R1 (6q23-24)
IFN-γ - R2 (21q22.1-22.2)
•
Toll-like receptors, tumor necrosis factor-α, and interleukin-10 gene polymorphisms in
risk of pulmonary tuberculosis and disease severity. Ma MJ, Xie LP, Wu SC, Tang F, Li H,
Zhang ZS, Yang H, Chen SL, Liu N, Liu W, Cao WC. Hum Immunol. 2010 Oct;71(10):100510. Epub 2010 Jul 30
•
TNF-α (tumor necrosis factor- α ) genis genotipis -857 C/T mniSvnelovani korelacia
filtvis tuberkulozis dabal riskTan
• polimorfuli variantis -863 A/C korelacia filtvis tuberkulozis SemTxvevebTan
Kkomplementis sistema
•
Major histocompatibility complex class III (C2, C4, factor B) and C3 gene variants in
patients with pulmonary tuberculosis. Senbagavalli P, Kumar N, Kaur G, Mehra NK,
Geetha ST, Ramanathan VD. Hum Immunol. 2011 Feb;72(2):173-8. Epub 2010 Nov 18.
• komplementis sistemis C2, C4, BF da C3 komponentebis genebis polimorfizmis Seswavla filtvis
tuberkulozis SemTxvevebSi
• kvlevis monacemebis Sedareba janmrTel sakontrolo jgufTan
• tuberkuloziT daavadebul jgufSi, sakontrolosTan SedarebiT, maRali aRmoCnda C4AQ0, BF*FA da
C3*F alelebis sixSire
•
A polymorphism in the inducible nitric oxide synthase gene is associated with tuberculosis. Gómez LM, Anaya JM,
Vilchez JR, Cadena J, Hinojosa R, Vélez L, Lopez-Nevot MA, Martín J. Tuberculosis (Edinb). 2007 Jul;87(4):288-94. Epub
2007 May 2.
•
Investigation of chromosome 17 candidate genes in susceptibility to TB in a South African population. Möller M, Nebel
A, Valentonyte R, van Helden PD, Schreiber S, Hoal EG. Tuberculosis (Edinb). 2009 Mar;89(2):189-94. Epub 2009 Jan 14.
•
me-17 qromosoma (17q11.2-12)
•
NOS2A (NO sinTetaza) polimorfizmebis korelacia tuberkulozTan sxvadasxva populaciebSi
•
tuberkulozis 800 SemTxveva
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NOS2A promotoris ori haplotipis (rs9282799 da rs8078340) mtkice korelacia tuberkulozis
SemTxvevbTan
•
mniSvnelovani gansxvaveba NOS2A CCTTT polimorfizmis mixedviT sakvlev da sakontrolo jgufebs
Soris, gansakuTrebiT _ mokle (8-11) ganmeorebadobebisTvis
•
Identification of tuberculosis susceptibility genes with human macrophage gene
expression profiles. Thuong NT, Dunstan SJ, Chau TT, Thorsson V, Simmons CP, Quyen NT,
Thwaites GE, Thi Ngoc Lan N, Hibberd M, Teo YY, Seielstad M, Aderem A, Farrar JJ, Hawn
TR. PLoS Pathog. 2008 Dec;4(12):e1000229. Epub 2008 Dec 5.
• 273 _ tuberkulozis SemTxveva
• 188 _ sakontrolo
• genis eqspresiis Sedareba ex vivo M.tuberculosis -iT stimulirebul da arastimulirebul
makrofagebSi
• qemotaqsisuri citokinuri ligadis CCL1 genis 6 saxis polimorfizmi iyo asocirebuli tuberkulozTan
5-lipoqsigenaza _ ALOX5 polimorfizmi
•
adamianis imunuri ujredebisa da citokinebis produqciis procesis modulatori _ imunuri ujredebis funqcionirebisa da
citokinebis maregulirebeli faqtorebis _ leikotrinebisa da lipoqsinebis _ biosinTezis gziT
•
ALOX5 (10q11.2) warmodgenilia 14 ekzoniT da 13 introniT da GC mdidari promotoriT
•
2179 da 256 fuZeTa wyvilis regionSi identificirebulia variabeluri tandemuri ganmeorebadobebi (50-GGGCGG30), romelic warmoadgens Sp1-transkrifciuli faqtoris bmis samiznes
•
tubekuloziT daavadebuli 1916 nacxdadebiTi pacienti ganas regionidan
•
ekzonuri alelis g.760A(Glu254Lys) arasinonimuri variabelobis mniSvnelovani korelacia tuberkulozis maRal
riskTan
•
naCvenebia populaciuri gansxvavebebi variabelobis sixSiris mixedviT
•
ALOX5 variants associated with susceptibility to human pulmonary tuberculosis. Florian
Herb, Thorsten Thye, Stefan Niemann, Edmund N.L. Browne, Margaret A. Chinbuah, John
Gyapong, Ivy Osei, Ellis Owusu-Dabo, Oliver Werz, Sabine Ru¨ sch-Gerdes, Rolf D.
Horstmann, Christian G. Meyer, Human Molecular Genetics, 2008, Vol. 17, No. 7 1052–106
• ALOX5 genotipebi:
homozigoturi veluri tipi _ ‘5/’5
heterozigoturi varianti _ ‘5/non5’
homozigoturi varianti _ ‘non5/ non5’
• tuberkuloziT daavadebuli pacientebis jgufSi, sakontrolosTan SedarebiT, mniSvnelovnad xSiri iyo genotipi
_ ‘5/non5’
imunitetTan asocirebuli gtf-aza (IRG-cila) intraujreduli paTogenebis autofagiis komponenti
• ori struqturuli subojaxebi:
1. GKS
2. GMS – Irgm1, Irgm2, Irgm3 – GKS cilebis gtf-azuri ciklis umTavres regulatorebad.
gansxvavebiT GKS cilebisagan, Seicaven meTionins lizinis nacvlad G1poziciaSi.
IRG cilis struqtura
N-terminaluri gtf bmuli domeni (G-domeni)
maRalvariabeluri C-terminaluri domeni
IRG genTa ojaxi
• tandemuri Tanmimdevrobebis 21 klasteri
(maT Soris _ fsevdogenebi) Tagvis genomSi, lokalizebuli
me-7 qromosomaze
• mxolod 2 asli adamianis genomSi:
1. IRGC – lokalizebulia me-19 qromosomaze 89%-iT identuri Tagvis Irgc – ar aris CarTuli imunutetSi
2. IRGM – lokalizebulia me-5 qromosomaze (5q33.1) da mniSvnelovan rols asrulebs tuberkulozis, tifis,
listeriozis, toqsoplazmozisa da qlamidiozis gamomwvevebis autofagur destruqciaSi
• adamianis IRGM m-rnm arsebobs xuTi, gansxvavebuli, 3′-splaisinguri izoformis (IRGM a–e)
saxiT, 30 nw sigrZis ekzoniT
• klonirebulia IRGM-domenis Semcveli calkeuli traskripti
• umoklesi transkripti IRGM(a) Seicavs 181 aminomJavis makodirebel erT did da oTx mcire ekzons
IRG genis struqtura
•
IRGM zogierTi polimorfizmi dakavSirebulia organizmis imunuri tolerantobis SemcirebasTan da intraujerduli
paTogenebiT inficirebis momatebul riskTan
•
IRGM polimorfuli varianti rs9637876 (−261 T) korelaciaSia Sesabamisi cilis eqspresiis zrdasTan da
organizmis warmatebul winaaRmdegobisunarTan M.tuberculosis da sxva aratuberkulozuri mikobaqteriebs
mimarT
•
IRGM genotipi – 2261TT (gansakuTrebiT _ homozigoturi mdgomareoba) dakavSirebulia IRGM cilis
eqspresiis gaZlierebasTan da tuberkulozisadmi SedarebiT mdgradobasTan, Sesabamisad _ negatiur korelaciaSia
M.tuberculosis gamowveul tuberkulozis SemTxvevebTan
•
IRGM alternatiuli splaisingi SesaZlo kritikuli meqanizmia transkriptis ujreduli donisTvis da Sesabamisad _
intraujreduli paTogenisadmi organizmis winaaRmdegobisunarianobisTvis
IRGM TanmimdevrobaTa struqturuli variantebisa da erTeuli nukleotiduri polimorfizmebis sqema
narinjisferiT aRniSnulia polimorfizmebi, romlebic cvlian genis eqspresias
• Alu-inserciis safuZvelze
IRGM warmoadgenda fsevdogens
50 milioni wlis win
IRGM evolucia
• Zveli da axali samyaros
maimunebSi IRGM arafunqciuria
• uZveles adamianSi IRGM funqcia
aRsda ERV9-elementis,
rogorc transkrifciis
maregulirebeli faqtoris,
genomSi integrirebis wyalobiT
• gibonebSi aRwerilia mocemuli genis,
rogorc funqciuri, ise
arafunqciuri mdgomareobebi
• ERV retrovirusuli elementebia,
daaxloebiT 14 subojaxs aerTianebs
da specifikuria primatebisaTvis
• ERV-elementebis roli adamianSi ucnobia, Tumca, zogierTi monacemis mixedviT, isini SeiZleba CarTulni
iyon egzogenuri virusebis prevenciis meqanizmSi
daskvna
• arsebuli monacemebi miuTiTeben maspinZeli organizmis genetikuri faqtorebis rolze tuberkuloziT
daavadebisadmi winaswarganwyobaSi
• tuberkulozisadmi genetikuri winaswarganwyobis meqanizmebSi CarTulia rogorc araspecifikuri, ise
specifikuri imunuri sistemis rgolebi
• tuberkuloziT daavadebaze pasuxismgebel kandidat genTa Sorisaa PRR receptorebis, citokinebis,
nitrogenoqsigenuri sinTezis, komplementis sitemis, vitamini D metabolizmis makodirebeli da sxva
imunomodulatoruli faqtorebis genebi
• aRniSnuli biologiuri sistemebis genetikuri regulaciis kvleva mniSvnelovani molekuluri meqanizmi
SeiZleba gaxdes, romelsac daefuZneba intervencia
KmimarTulebis perspeqtiva
• tuberkulozuri infeqciuri procesis ganviTarebasTan dakavSirebuli genetikuri meqanizmebis dadgena
• maspinZeli organizmis resursebze damyarebuli axali, prevenciuli, RonisZiebebis ganviTareba
• imunointervenciaze dafuZnebuli Terapiuli strategiebis SemuSaveba
• masobrivi skriningi tuberkulozis, genetikurad ganpirobebuli, risk-jgufebis gamovlenis mizniT