ﻲﻠﭘ طﺎﺒﺗرا ﻢﺴﻴﻓرﻮﻣ
ﻪﺒﺷ هﺪﻧﺮﻳﺬﭘ ﻲﻜﻴﺘﻧژ يﺎﻫ 4 Toll
(TLR4) ﻪﺑ ﻼﺘﺑا داﺪﻌﺘﺳا و
يﻮﻳر ﻞﺳ
ﻚﻴﺟﺎﺗ ردﺎﻧ ﺮﺘﻛد*
I
يﺮﻴﺼﻧ ﺎﺿرﺪﻤﺤﻣ
II
يﺮﻔﻌﺟ ﺪﻤﺤﻣ
II
يﻮﺳﻮﻣ هﺮﻫﺎﻃ ﺮﺘﻛد III
ﺎﻴﻧﺮﻓ ﺎﺴﻳﺮﭘ ﺮﺘﻛد
IV
مﺪﻘﻣ ﻚﻟﺎﺳ ﺎﺿﺮﻴﻠﻋ ﺮﺘﻛد
III
نﺎﻴﻜﻨﺳ ﻲﺒﺘﺠﻣ ﺮﺘﻛد V
هﺪﻴﻜﭼ
و ﻪﻨﻴﻣز فﺪﻫ TLR2: و TLR4
هﺪﻧﺮﻳﺬﭘ هداﻮﻧﺎﺧ زا ﻲﻳﺎﻀﻋا
يﺎﻫ ﻪﺒﺷ
و ﻲﻳﺎﺳﺎﻨﺷ رد ار ﻲﻤﻬﻣ ﺶﻘﻧ و هدﻮﺑ Toll
يﺮﺘﻛﺎـﺑﻮﻜﻳﺎﻣ ﻪـﻴﻠﻋ ﻲـﻨﻤﻳا ﺦـﺳﺎﭘ نآ ﺐﻗﺎﻌﺘﻣ
ﺎـﻫ ﺎـﻔﻳا ﻲـﻣ ﺪـﻨﻨﻛ . 2 ﻲـﻠﭘ ﻢﺴـﻴﻓرﻮﻣ
نژ ياﺮـﺑ ﻞﻧﻮﻴﺴـﻜﻧﻮﻓ
يﺎـﻫ TLR2
(Arg677Trp CÆT, Arg753Gln GÆA) TLR4 و
Asp299Gly AÆG Thr399Ile CÆT) (
ﺎﺑ ﺮﺑ ﻲﻔﻨﻣ ﺮﺛا
هدﻮﺑ ﻂﺒﺗﺮﻣ ﺎﻬﻧآ دﺮﻜﻠﻤﻋ
،ﺪﻧا
يﺮﺘﻛﺎﺑﻮﻜﻳﺎﻣ ﺮﺑاﺮﺑ رد نﺎﺑﺰﻴﻣ ﻲﺗاذ ﻲﻨﻤﻳا ﺦﺳﺎﭘ ﺖﺳا ﻦﻜﻤﻣ وﺮﻨﻳا زا
ﺎﻫ راﺮﻗ ﺮﻴﺛﺄﺗ ﺖﺤﺗ ار
ﺪﻨﻫد .
ﺖﻧﺎﻳراو ﻲﺳرﺮﺑ ﻪﻌﻟﺎﻄﻣ ﻦﻳا زا فﺪﻫ
يﺎﻫ ﻲﻜﻴﺘﻧژ و TLR2 ﻞـﺳ ﻪﺑ ﻼﺘﺒﻣ ﻲﻧاﺮﻳا نارﺎﻤﻴﺑ زا ﻲﺘﻴﻌﻤﺟ رد TLR4
ﻟﺎﺳ داﺮﻓا ﺎﺑ ﺎﻬﻧآ ﻪﺴﻳﺎﻘﻣ و يﻮﻳر ﺖﺳا هدﻮﺑ ﻢ
.
ﻲﺳرﺮﺑ شور :
يور ﺮﺑ 96 و رﺎﻤﻴﺑ 122 ﻪـﻌﻟﺎﻄﻣ ﻚـﻳ ﻢﻟﺎـﺳ ﺪﻫﺎﺷ دﺮﻓ
"
درﻮـﻣ - ﺪﻫﺎـﺷ
"
ﺪـﺷ مﺎـﺠﻧا .
ﻦﻴـﻴﻌﺗ شور
ﺪﻳﺪﺟ ﻚﻴﻨﻜﺗ ﻚﻳ ﻪﻳﺎﭘ ﺮﺑ ﭗﻳﺎﺗﻮﻧژ PCR-SSP
ﺖﻓﺮﮔ ترﻮﺻ .
ﻂﺳﻮﺗ رﻮﻛﺬﻣ يﺎﻫ ﻢﺴﻴﻓرﻮﻣ ﻲﻠﭘ ﻲﭙﻳﺎﺗﻮﻧژ و ﻲﻠﻟآ ﻊﻳزﻮﺗ
ﺷ ﻪﺴﻳﺎﻘﻣ لﺮﺘﻨﻛ داﺮﻓا و نارﺎﻤﻴﺑ يﺎﻫ هوﺮﮔ رد ﺮﺸﻴﻓ ﻖﻴﻗد نﻮﻣزآ ﺪﻧﺪ
.
ﻪﺘﻓﺎﻳ ﺎﻫ :
ﻞﻟآ ﻲﻧاواﺮﻓ
يﺎﻫ ﺖﻧﺎﻳراو
) TLR4
Gly299 Ile399و
( ترﻮﺻ ﻪﺑ نارﺎﻤﻴﺑ رد ﻲﻨﻌﻣ
راد داﺮـﻓا زا ﺮﺘﺸـﻴﺑ ي
دﻮـﺑ لﺮـﺘﻨﻛ هوﺮﮔ )
028 / 0 P value=
، 66 / 2 OR = ، 9 / 2 vs % 3 / 7 : % Gly299 و 022 / 0 P value = ، 26 / 5 OR= ، 8 / 0 %
2vs / 4 Ile399 : % ( . درﻮﻣ رد ﻲﻠﭘ ﻢﺴﻴﻓرﻮﻣ Arg753Gln TLR2نژ
، توﺎﻔﺗ ﭻﻴﻫ ﻲﻨﻌﻣ
راد رﺎﻤﻴﺑ و ﺪﻫﺎﺷ هوﺮﮔ ﻦﻴﺑ ي
ﺪﺸﻧ هﺪﻫﺎﺸﻣ )
05 /
>0 ؛ p 0 vs % 8 / 0 (%
) . ﻲﻠﭘ ﺮﮕﻳد ﻢﺴﻴﻓرﻮﻣ TLR2
(Arg677Trp) درﻮـﻣ دراﻮﻣ زا ماﺪﻛ ﭻﻴﻫ رد ﺰﻴﻧ
ﺪﻳدﺮﮕﻧ ﺖﻓﺎﻳ ﻪﻌﻟﺎﻄﻣ .
ﻪﺠﻴﺘﻧ يﺮﻴﮔ :
نﺎﺸﻧ ﺎﻣ ﺞﻳﺎﺘﻧ ﻲﻣ
ﻪﻛ ﺪﻨﻫد ﻲﻠﭘ ﻢﺴﻴﻓرﻮﻣ يﺎﻫ ﻲﻜﻴﺘﻧژ TLR4
يرﺎـﻤﻴﺑ دﺎـﺠﻳا ﺮﻄﺧرد ﺖﺳا ﻦﻜﻤﻣ ﻞـﺳ
ﺪﻨﺷﺎﺑ ﺮﺛﺆﻣ مﻮﻳﺮﺘﻛﺎﺑﻮﻜﻳﺎﻣ ﺎﺑ ﻪﻬﺟاﻮﻣ زا ﺲﭘ .
ﻲـﻜﻴﺘﻧژ يﺎـﻫ ﺖـﻧﺎﻳراو ﻢﻛ رﺎﻴﺴﺑ ﻲﻧاواﺮﻓ ﻦﻳا ﺮﺑ هوﻼﻋ رد ﺰـﻴﻧ TLR2
ﺪﻳدﺮﮔ رﺎﻜﺷآ ﻲﻧاﺮﻳا ﺖﻴﻌﻤﺟ .
هژاوﺪﻴﻠﻛ ﺎﻫ : 1 - ﻞﺳ 2 - ﻲﻠﭘ ﻢﺴﻴﻓرﻮﻣ ﻲﻜﻴﺘﻧژ 3 - هﺪﻧﺮﻳﺬﭘ يﺎﻫ Tollﻪﺒﺷ 4 - ﻲﻧاﺮﻳا ﺖﻴﻌﻤﺟ
ﺖﻓﺎﻳرد ﺦﻳرﺎﺗ :
14 / 7 / 87
، ﻳرﺎﺗ شﺮﻳﺬﭘ ﺦ :
26 / 12 / 87
ﻪﻣﺪﻘﻣ
(TB)ﻞﺳ ،ﻲﻧﺎﻬﺟ ﺖﺷاﺪﻬﺑ رد ﻲﺳﺎﺳا ﻞﻜﺸﻣ ﻚﻳ ناﻮﻨﻋ ﻪﺑ
ـﻣ گﺮـﻣ مﺎـﻛ ﻪـﺑ ار ﺮﻔﻧ نﻮﻴﻠﻴﻣ ود زا ﺶﻴﺑ ﻪﻧﺎﻴﻟﺎﺳ ﻲ
ﺪﺸـﻛ .
ﺎــﺑ ﺖـﻧﻮﻔﻋ ﺲﻳزﻮــﻟﻮﻛﺮﺑﻮﺗ مﻮﻳﺮﺘﻛﺎـﺑﻮﻜﻳﺎﻣ
(M.TB) ﻞــﻣﺎﻋ
دﺎﺠﻳا مﻮﺳ ﻚﻳ رد ﺎﺒﻳﺮﻘﺗ ،ﻞﺳ ﺖﻴﻌﻤﺟ
ﻲﻟو هدﺎﺘﻓا قﺎﻔﺗا ﺎﻴﻧد
دوﺪﺣ ﻂﻘﻓ 10
% رد داﺮﻓا ﻦﻳا زا ضﺮﻌﻣ رد دﻮﺧ تﺎﻴﺣ لﻮﻃ
زوﺮﺑ ﺮﻄﺧ TB
ﺪﻧراد راﺮﻗ
).
1
توﺎﻔﺗ (
يﺎﻫ هدﻮﻟآ داﺮﻓا ﻲﻜﻴﺘﻧژ
ﺮﺛﺆﻣ ﺖﻧﻮﻔﻋ ﺖﺒﻗﺎﻋ رد ﻲﻣ
ﺪﺷﺎﺑ .
ﺺﺧﺎﺷ دﻮﺟو ﻦﻳا ﺎﺑ
يﺎـﻫ
ﻪﺑ ﻼﺘﺑا داﺪﻌﺘﺳا ﻲﻜﻴﺘﻧژ
،TB رد ﻲـﻨﻤﻳا ﻢﺘﺴـﻴﺳ ﻪﻛ يداﺮﻓا
ﻪﺘﺧﺎﻨـﺷ ﺎـﻧ يدﺎـﻳز راﺪـﻘﻣ ﻪـﺑ دراد ﻲﻤﻟﺎـﺳ دﺮـﻜﻠﻤﻋ ﺎﻬﻧآ ﺪﻨﺘﺴﻫ . نژ
ﺎﻫﺪﻧور رد ﻞﻴﺧد يﺎﻫ ياﺮﺑ ﻪﻛ ﻚﻳژﻮﻟﻮﻧﻮﻤﻳا ي
ﺖﻧﻮﻔﻋ لﺮﺘﻨﻛ يروﺮﺿ M.TB
ﻲﻣ ﺪﻨﺷﺎﺑ
، ﻞﻣاﻮﻋ ناﻮﻨﻋ ﻪﺑ
بﻮﺴﺤﻣ يرﺎﻤﻴﺑ هﺪﻨﻨﻛ ﺪﻌﺘﺴﻣ ﻲﻣ
ﺪﻧدﺮﮔ
).
2
(
ﻪﺻﻼﺧ ﻪﻟﺎﻘﻣ ﻦﻳا
يا زا ﺖﺳا نﺎﻳﺎﭘ ﻪﻣﺎﻧ و يﻮـﺳﻮﻣ هﺮﻫﺎـﻃ ﺮـﺘﻛد و ﻚـﻴﺟﺎﺗ ردﺎـﻧ ﺮـﺘﻛد ﻲﻳﺎﻤﻨﻫار ﻪﺑ ﺪﺷرا ﻲﺳﺎﻨﺷرﺎﻛ ﻪﺟرد ﺖﻓﺎﻳرد ﺖﻬﺟ يﺮﻴﺼﻧ ﺎﺿرﺪﻤﺤﻣ يﺎﻗآ
ﺮﺘﻛد هروﺎﺸﻣ لﺎﺳ ،نﺎﻴﻜﻨﺳ ﻲﺒﺘﺠﻣ ﺮﺘﻛد و ﺎﻴﻧﺮﻓ ﺎﺴﻳﺮﭘ ﺮﺘﻛد ،مﺪﻘﻣ ﻚﻟﺎﺳ ﺎﺿﺮﻴﻠﻋ
1387 .
ﻲﻧﺎـﻣرد ﻲﺘـﺷاﺪﻬﺑ تﺎﻣﺪـﺧ و ﻲﻜـﺷﺰﭘ مﻮـﻠﻋ هﺎﮕﺸـﻧاد ،ﻲﻜﺷﺰﭘ هﺪﻜﺸﻧاد ،يژﻮﻟﻮﻧﻮﻤﻳا تﺎﻘﻴﻘﺤﺗ ﺰﻛﺮﻣ و هوﺮﮔ ،ﻚﻴﺘﻧژﻮﻧﻮﻤﻳا و ﺪﻧﻮﻴﭘ يژﻮﻟﻮﻧﻮﻤﻳا ﺶﺨﺑ رﺎﻴﺸﻧاد(I
ناﺮﻳا ،ناﺮﻬﺗ ،ناﺮﻳا *)
لوﺆﺴﻣ ﻒﻟﺆﻣ (
ﺪﺷرا ﻲﺳﺎﻨﺷرﺎﻛ(II ﻲﺘـﺷاﺪﻬﺑ تﺎﻣﺪـﺧ و ﻲﻜﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ،ﻲﻜﺷﺰﭘ هﺪﻜﺸﻧاد ،يژﻮﻟﻮﻧﻮﻤﻳا تﺎﻘﻴﻘﺤﺗ ﺰﻛﺮﻣ و هوﺮﮔ ،ﻚﻴﺘﻧژﻮﻧﻮﻤﻳا و ﺪﻧﻮﻴﭘ يژﻮﻟﻮﻧﻮﻤﻳا ﺶﺨﺑ ،
ناﺮﻳا ،ناﺮﻬﺗ ،ناﺮﻳا ﻲﻧﺎﻣرد
( (III ﻋ هﺎﮕﺸﻧاد ،ﻲﻜﺷﺰﭘ هﺪﻜﺸﻧاد ،يژﻮﻟﻮﻧﻮﻤﻳا تﺎﻘﻴﻘﺤﺗ ﺰﻛﺮﻣ و هوﺮﮔ ،ﻚﻴﺘﻧژﻮﻧﻮﻤﻳا و ﺪﻧﻮﻴﭘ يژﻮﻟﻮﻧﻮﻤﻳا ﺶﺨﺑ دﺎﺘﺳا ﻲﻧﺎـﻣرد ﻲﺘـﺷاﺪﻬﺑ تﺎﻣﺪـﺧ و ﻲﻜـﺷﺰﭘ مﻮﻠ
ناﺮﻳا ،ناﺮﻬﺗ ،ناﺮﻳا
ناﺮﻳا ،ناﺮﻬﺗ ،ﻲﺘﺸﻬﺑ ﺪﻴﻬﺷ ﻲﻜﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ،ﻲﻜﺷﺰﭘ هﺪﻜﺸﻧاد ،يرﻮﺸﻧاد ﺢﻴﺴﻣ نﺎﺘﺳرﺎﻤﻴﺑ ،يژﻮﻟﻮﻳﺮﺘﻛﺎﺑﻮﻜﻳﺎﻣ هﺎﮕﺸﻳﺎﻣزآ ،رﺎﻳدﺎﺘﺳا(IV ا ،ﺪﻬﺸﻣ ،ﺪﻬﺸﻣ ﻲﻜﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ،ﻲﻜﺷﺰﭘ هﺪﻜﺸﻧاد ،يژﻮﻟﻮﻧﻮﻤﻳا هوﺮﮔ رﺎﻳدﺎﺘﺳا (V ناﺮﻳ
رد ﻲﺗاذ ﻲﻨﻤﻳا
مﻮﻳﺮﺘﻛﺎﺑﻮﻜﻳﺎﻣ ﺎﺑ ﻪﻠﺑﺎﻘﻣ ﻲـﻤﻬﻣ ﺶـﻘﻧ
دراد هﺪﻬﻋ ﺮﺑ .
،نﺪـﺑ ﻪﺑ ﺲﻔﻨﺗ هار زا ﻞﺳ ﻞﻴﺳﺎﺑ دورو ﺎﺑ
ژﺎﻓوﺮﻛﺎﻣ
يﺎﻫ ﻖـﻳﺮﻃ زا ﻲﻟﻮﺋﻮﻟآ هﺪـﻧﺮﻳﺬﭘ
يﺎـﻫ ﻲﻳﺎﺸـﻏ
هﺪـﻧﺮﻳﺬﭘ ﺪـﻨﻧﺎﻣ ﻲﻔﻠﺘﺨﻣ
يﺎـﻫ ،زﻮﻧﺎـﻣ هﺪـﻧﺮﻳﺬﭘ ،نﺎـﻤﻠﭙﻤﻛ
هﺪﻧﺮﻳﺬﭘ يﺎﻫ هﺪﻨﻨﻛ يزﺎﺴﻛﺎﭘ
هﺪـﻧﺮﻳﺬﭘ و
يﺎـﻫ ﻪﺒـﺷ Toll
(TLRs) نآ ﻊـﻠﺑ ﺮـﺑ هوﻼﻋ و هدﺮﻛ ﻲﻳﺎﺳﺎﻨﺷ ار يﺮﺘﻛﺎﺑ
ﻪــﻴﻠﻋ عﺎــﻓد مﺪــﻘﻣ ﻂــﺧ ،ﻲﺑﺎــﻬﺘﻟا ﺦــﺳﺎﭘ ﻚــﻳ دﺎــﺠﻳا ﺎــﺑ
ﻞﻜﺷ ار مﻮﻳﺮﺘﻛﺎﺑﻮﻜﻳﺎﻣ ﻲﻣ
ﺪﻨﻫد TLR .
هداﻮﻧﺎـﺧ ﺎﻫ
يا زا
هﺪﻧﺮﻳﺬﭘ يﺎﻫ يﺎـﻫﻮﮕﻟا زا ﻲﻌﻴـﺳو ﻒﻴﻃ ﻪﻛ هدﻮﺑ ﻲﻳﺎﺸﻏ
ﺺﻴﺨﺸﺗ ار ﻲﺑوﺮﻜﻴﻣ ﻲﻣ
ﺪـﻨﻫد . نﻮـﻨﻛ ﺎـﺗ 13
رد ﻮﻀـﻋ
ﻪﻛ هﺪﺷ ﻲﻳﺎﺳﺎﻨﺷ هداﻮﻧﺎﺧ ﻦﻳا 10
ﺎﻬﻧآ زا دﺪﻋ (TLR1-
TLR10) ﺪــﻧراد دﻮــﺟو نﺎﺴــﻧا رد
. ﻲﻣﺎــﻤﺗ يﺎــﻫTLR
ﻪـﻛ ﺪﻨﺘﺴﻫ ﻲﻟﻮﻠﺳ جرﺎﺧ ﻦﻴﻣود ﻚﻳ ياراد هﺪﺷ ﻪﺘﺧﺎﻨﺷ ﻲﻟاﻮــﺗ زا يﺎــﻫ
ﻦﻴــﺳﻮﻟ ﻪــﻨﻴﻣآ ﺪﻴــﺳا زا ﻲــﻨﻏ يراﺮــﻜﺗ
(Leucine rich repeats) ﻞﻴﻜﺸـﺗ
ﻲـﻣ ﻞـﻤﻋ رد و دﻮـﺷ
دراد ﺖــﻟﺎﺧد ﺪــﻧﺎﮕﻴﻟ ﻲﻳﺎــﺳﺎﻨﺷ .
ﻦﻴــﻣود ﻚــﻳ هوﻼــﻋ ﻪــﺑ
ﻤﻫ ﻪــﻛ ﻲﻤــﺳﻼﭘﻮﺘﻴﺳ رد مﺎــﻴﭘ لﺎــﻘﺘﻧا ﻦﻴــﻣود گﻮــﻟﻮ
ﻦﻴﻛﻮﻟﺮﺘﻨﻳا هﺪﻧﺮﻳﺬﭘ -
(IL-1R)1 و هدﻮﺑ
) TIR (Toll/IL-
1 Receptor لﻮﻠـﺳ ﻞﺧاد ﻪﺑ مﺎﻴﭘ لﺎﺳرا ﻞﻤﻋ ،دراد مﺎﻧ
مﺎﺠﻧا ار ﻲﻣ
ﺪﻫد .
نژ ﻲﺘﻧآ نﺎﻴﻣ زا
يﺎـﻫ
مﻮﻳﺮﺘﻛﺎـﺑﻮﻜﻳﺎﻣ
ﻲـــﻣ تراﺮـــﺣ ﻪـــﺑ سﺎﺴـــﺣ رﻮﺘﻛﺎـــﻓ ﻚـــﻳ ﻪـــﺑ ناﻮـــﺗ
ﺪــﻧﺎﮕﻴﻟ ﻪــﻛ مﻮﻳﺮﺘﻛﺎــﺑﻮﻜﻳﺎﻣ ﻲــﻣ TLR4
ﻦﻴــﻨﭽﻤﻫ ،ﺪــﺷﺎﺑ
،نﺎﻧﺎﻣ ﻮﻨﻴﺑارآﻮﭙﻴﻟ لﻮﺘﻳزﻮﻨﻳاﻮﻳﺎـﻣ ﻞﻳﺪﻴﺗﺎﻔﺴﻓ ،نﺎﻧﺎﻣﻮﭙﻴﻟ
ﻦﻴﺌﺗوﺮﭘﻮـﭙﻴﻟ ،ﺪﻳزﻮﻧﺎﻣ
19
لﻮـﻠﺤﻣ ﻲﻧﻮـﺘﻟادﻮﻠﻴﻛ
،LpqH
ﻦﻴﺌﺗوﺮﭘﻮﭙﻴﻟ ﻦﻴﺌﺗوﺮﭘﻮﭙﻴﻟ و LprG
ﻪﻛ دﺮﻛ هرﺎﺷا LprA
ﻂــﺳﻮﺗ ﻲﻳﺎــﺳﺎﻨﺷ TLR2
ﻲــﻣ ﺪﻧﻮــﺷ
).
8 - 3
ﻲﻳﺎــﺳﺎﻨﺷ (
ﻂــﺳﻮﺗ مﻮﻳﺮﺘﻛﺎــﺑﻮﻜﻳﺎﻣ
ﻪــﺑ ﺮــﺠﻨﻣ ﺎــﻫTLR
ﻊﻳﺎــﻗو
ﺎﻬﻧ رد ﻪــﻛ ﻪﺘﺸــﮔ ﻲﻤــﺳﻼﭘﻮﺘﻴﺳ ﺖــﻴﻟﺎﻌﻓ ﺐــﺟﻮﻣ ﺖــﻳ
رﻮﺘﻛﺎﻓ يﺎﻫ ﻲﺴﻳﻮﻧور ﺮـﻴﻈﻧ
و NFκB لﺎـﻘﺘﻧا و ،AP-1
ﻚﻳﺮﺤﺗ و ﻪﺘﺴﻫ ﻪﺑ ﺎﻬﻧآ ﻲﺴﻳﻮﻧور
نژ ﺪﻨﻧﺎﻣ ﻲﻳﺎﻫ نژ زا
ﻦﻳﺎﻛﻮﺘﻳﺎﺳ
لﻮﻜﻟﻮﻣ ،ﺎﻫ ﻦﻳﺎﻛﻮﻤﻛ ،ﻲﺑﺎﻬﺘﻟا يﺎﻫ
يﺎﻫ ﻚـﻤﻛ
لﻮـــﻜﻟﻮﻣ و ﻲـــﻜﻳﺮﺤﺗ ﺒﺴـــﭼ يﺎـــﻫ
ﻲﮔﺪﻨ ﻲـــﻣ ددﺮـــﮔ . ﻦﻳﺎﻛﻮﺘﻳﺎﺳ
يﺎﻫ ﺐﺒـﺳ ﺎـﻫژﺎﻓوﺮﻛﺎﻣ ﻂـﺳﻮﺗ هﺪـﺷ ﺪـﻴﻟﻮﺗ
ﺮﻳﺎﺳ ﻲﻧاﻮﺧاﺮﻓ لﻮﻠﺳ
يﺎﻫ لﻮﻠﺳ ﻞﻣﺎﺷ ﻲﺗاذ ﻲﻨﻤﻳا يﺎـﻫ
ﻲﻌﻴﺒﻃ هﺪﻨﺸﻛ
(NK)
ﺖﻴﺳﻮﻔﻨﻟ و
يﺎـﻫ T ﻊـﺿﻮﻣ ﻪـﺑ γδ
ﺮﮔ د
ﻦﻳﺎﻛﻮﺘﻳﺎﺳ ﺢﺷﺮﺗ ﺎﺑ دﻮﺧ ﻪﺑﻮﻧ ﻪﺑ ﻪﻛ هﺪﻳ يﺎـﻫ
لﺎـﻌﻓ
مﻮﻳﺮﺘﻛﺎــﺑﻮﻜﻳﺎﻣ يزﺎــﺳدﻮﺑﺎﻧ ﺖــﻴﻓﺮﻇ ،ژﺎــﻓوﺮﻛﺎﻣ هﺪــﻨﻨﻛ لﻮﻠــﺳ ﻦــﻳا ﻂــﺳﻮﺗ ﺎــﻫ
ﺶﻳاﺰــﻓا ار ﻲــﻣ
ﺪــﻨﻫد . ﺪﻫاﻮــﺷ
رد ﻪﻛ ﺪﻨﺘﺴﻫ ﻪﺘﻜﻧ ﻦﻳا ﺪﻳﺆﻣ ﻚﻳژﻮﻟﻮﻴﻣﺪﻴﭘا 70
% ،دراﻮـﻣ
هدﻮﺑ ﻲﻓﺎﻛ ﻲﻳﺎﻬﻨﺗ ﻪﺑ ﻲﺗاذ ﻲﻨﻤﻳا ﺮﺑ ﻲﻨﺘﺒﻣ ﻲﺑﺎﻬﺘﻟا ﺦﺳﺎﭘ
و ﻲﻣ يدﻮﺑﺎـﻧ ﺐﺒﺳ ﺪﻧاﻮﺗ
M.TB
ددﺮـﮔ . زا يرﺎﻴﺴـﺑ رد
سﺎﻤﺗ ﻦﻴﻟﻮﻠﺴﻣ ﺎﺑ ﻪﻛ يداﺮﻓا ﻢﻴﻘﺘﺴﻣ
ﻪﺘﺷاد
،ﺪﻧا نﻮـﻣزآ
ﺖﺒﺜﻣ PPD ﻲﻤﻧ
ﻞـﺳ ﻞﻴـﺳﺎﺑ فﺬﺣ ﺮﺑ دﻮﺧ ﻦﻳا ﻪﻛ دﻮﺷ
لﻮﻠـــﺳ ﺖﻛرﺎﺸـــﻣ نوﺪـــﺑ يﺎـــﻫ
هﺮﻃﺎـــﺧ دﺎـــﺠﻳا و T
ﺖــﻟﻻد ﻚــﻳژﻮﻟﻮﻧﻮﻤﻳا دراد
).
9
دراﻮــﻣ ﺮﻳﺎــﺳ رد (
، ﺦــﺳﺎﭘ
ﻲـﺘﻧآ ﻪﺿﺮﻋ زا ﺲﭘ و هدﻮﺒﻧ ﻲﻓﺎﻛ ﻲﻳﺎﻬﻨﺗ ﻪﺑ ﻲﺗاذ ﻲﻨﻤﻳا نژ يﺎــﻫ
لﻮﻠــﺳ ﻂــﺳﻮﺗ يﺮﺘﻛﺎــﺑ يﺎــﻫ
ﻪــﺑ ﻲﺘﻳرﺪــﻧد
ﺖﻴﺳﻮﻔﻨﻟ
يﺎﻫ T
هﺮﮔ رد دﻮﺟﻮﻣ
يﺎـﻫ ،ﻲﻌـﺿﻮﻣ يوﺎـﻔﻨﻟ
دﺎﺠﻳا ﻲﺑﺎﺴﺘﻛا ﻲﻨﻤﻳا ﺦﺳﺎﭘ ﻲﻣ
دﻮـﺷ . زا ﺲـﭘ ﻪـﺠﻴﺘﻧ رد
ﺖﻴﺳﻮﻔﻨﻟ ﺮﻴﺜﻜﺗ
يﺎﻫ T
ﻌﻓ ،ﻪـﻳر ﻪـﺑ ﺎﻬﻧآ تﺮﺟﺎﻬﻣ و ﺖـﻴﻟﺎ
لﻮﻠﺳ يﺎـﻫ TH1 يﺮـﻴﮔ ﻞﻜـﺷ ﻪـﺑ ﺮـﺠﻨﻣ ﺎـﻫژﺎﻓوﺮﻛﺎﻣ و
ﺖﻧﻮﻔﻋ نﺪﺷ دوﺪﺤﻣ و ﺎﻣﻮﻟﻮﻧاﺮﮔ ﻲﻣ
ددﺮﮔ .
ﻲــﻠﭘ ﻢﺴــﻴﻓرﻮﻣ يﺎــﻫ
نژ ﻒــﻠﺘﺨﻣ ﻲﺣاﻮــﻧ رد ﻲــﻜﻴﺘﻧژ
ﻲﻣ راﺬﮔﺮﻴﺛﺎﺗ ﺮﻈﻧ درﻮﻣ لﻮﻜﻟﻮﻣ دﺮﻜﻠﻤﻋ ﺎﻳ نﺎﻴﺑ ﺮﺑ ﺪﻨﻧاﻮﺗ
ﺪﻨﺷﺎﺑ . ﻦﻳا زا يرﺎﻴﺴﺑ ﻲﻠﭘ
ﻢﺴﻴﻓرﻮﻣ
ﺎﻫ نژ رد يﺎﻫ ﻞـﻴﺧد
ﻤﻳا ﻪﻠﻤﺟ زا ﻲﻨﻤﻳا ﺦﺳﺎﭘ رد
هﺪـﺷ ﻲﻳﺎـﺳﺎﻨﺷ ﻲـﺗاذ ﻲﻨ
ﺪـﻧا .
لﻮﻜﻟﻮﻣ ﻦﻳا رد ﻲﺋﺰﺟ تاﺮﻴﻴﻐﺗ
ﺎﻫ يدﺎﻳز ﺮﻴﺛﺎﺗ ﺖﺳا ﻦﻜﻤﻣ
ﺦﺳﺎﭘ رد يﺎﻫ عﺎﻓد ﺎﻳ و بﺎﻬﺘﻟا يﺮﻴﮔ ﻞﻜﺷ ياﺮﺑ ﻪﻛ يﺪﻌﺑ
ﺪـﺷﺎﺑ ﻪﺘﺷاد ،ﺪﻨﺘﺴﻫ يروﺮﺿ نﺎﺑﺰﻴﻣ .
درﻮـﻣ رد TLR2
موزﻮــﻣوﺮﻛ ﺪــﻨﻠﺑ يوزﺎــﺑ يور ﺮــﺑ نآ نژ ﻪــﻛ 4
ﻊــﻗاو
ﻦﻳزﻮﺘﻴــــﺳ ﺪــــﻴﺗﻮﺌﻠﻛﻮﻧ ﻲﻨﻳﺰﮕﻳﺎــــﺟ ،هﺪــــﺷ رد (C)
ﺖــﻴﻌﻗﻮﻣ 2180
نوﺰــﮔا رد 3
ﻦﻴــﻤﻴﺗ ﺎــﺑ ﻪــﺑ ﺮــﺠﻨﻣ (T)
ﻦﻴـﻧژرآ ﻪﻨﻴﻣآﺪﻴﺳا ﻞﻳﺪﺒﺗ (Arg)
نﺎـﻓﻮﺘﭙﻳﺮﺗ ﻪـﺑ (Trp)
رد
نوﺪــﻛ 677 هﺪــﺷ (Arg677Trp) ﻦﻴﻧاﻮــﮔ ﻲﻨﻳﺰﮕﻳﺎــﺟ و
ﻦﻴﻧدآ ﺎﺑ (G) ﺖﻴﻌﻗﻮﻣ رد (A)
2251 نوﺰـﮔارد 3
ﺚـﻋﺎﺑ
ﻦﻴﻧژرآ ﻞﻳﺪﺒﺗ (Arg)
ﻦﻴﻣﺎﺗﻮﻠﮔ ﻪﺑ (Gln)
نوﺪـﻛ رد 753
(Arg753Gln) ﻲــﻣ
ددﺮــﮔ . زا ﻲــﻠﭘ ﻢﺴــﻴﻓرﻮﻣ يﺎــﻫ
ﻚــﺗ
ﻊﻳﺎــﺷ يﺪــﻴﺗﻮﺌﻠﻛﻮﻧ
يوزﺎــﺑ يور ﺮــﺑ نآ نژ ﻪــﻛ TLR4
موزﻮﻣوﺮﻛ ﺪﻨﻠﺑ 9
،دراد راﺮﻗ ﻲﻣ
ﻪﺑ ناﻮﺗ Asp299Gly
و
Thr399Ile ﺪــﻴﺗﻮﺌﻠﻛﻮﻧ لوا درﻮــﻣ رد ﻪــﻛ دﺮــﻛ هرﺎــﺷا
ﻦﻴﻧدآ ﺖﻴﻌﻗﻮﻣ رد (A)
896 نوﺰﮔا رد 3
ﻦﻴﻧاﻮـﮔ ﺎﺑ (G)
ﻳزﻮﺘﻴﺳ ﺪﻴﺗﻮﺌﻠﻛﻮﻧ ﺰﻴﻧ مود درﻮﻣ رد و هﺪﺷ ﻦﻳﺰﮕﻳﺎﺟ ﻦ
ﺖﻴﻌﻗﻮﻣ رد (C) 1196
نوﺰﮔا رد 3
ﻦﻴـﻤﻴﺗ يﺎـﺟ ﻪﺑ (T)
راﺮﻗ ﻲﻣ دﺮﻴﮔ .
طﺎـﺒﺗرا ﻲـﺳرﺮﺑ ﻪـﻌﻟﺎﻄﻣ ﻦﻳا رد ﺎﻣ فﺪﻫ
ﻲﻠﭘ ﻢﺴﻴﻓرﻮﻣ
يﺎﻫ درﻮـﻣ رد هﺪـﺷ ﺮﻛذ و TLR2
TLR4
هدﻮـﺑ ﻲـﻧاﺮﻳا ﺖـﻴﻌﻤﺟ رد يﻮﻳر ﻞﺳ ﻪﺑ ﻼﺘﺑا داﺪﻌﺘﺳا ﺎﺑ
ﺖﺳا .
شور ﻲﺳرﺮﺑ
هوﺮﮔ يﺎﻫ ﺪﻫﺎﺷ رﺎﻤﻴﺑ و
ترﻮــﺻ ﻪــﺑ ﻪــﻌﻟﺎﻄﻣ ﻦــﻳا Case-control
يور ﺮــﺑ 96
رﻮﻳﺮﻬـﺷ ﻲﻧﺎـﻣز ﻪﻠـﺻﺎﻓ رد ﻪـﻛ يﻮﻳر ﻞﺳ ﻪﺑ ﻼﺘﺒﻣ رﺎﻤﻴﺑ لﺎــﺳ هﺎــﻣ ﻦــﻤﻬﺑ ﺖــﻳﺎﻐﻟ هﺎــﻣ 1386
ﻲﻧﻮــﻔﻋ ﺶــﺨﺑ رد ،
يرﻮﺸﻧاد ﺢﻴﺴﻣ نﺎﺘﺳرﺎﻤﻴﺑ )
ﺪﻴﻬﺷ ﻲﻜﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد
ﻲﺘﺸﻬﺑ (
راﺮـﻗ ﻞـﺳ نﺎـﻣرد ﺖـﺤﺗ و يﺮﺘﺴـﺑ ،ناﺮﻬﺗ ﺮﻬﺷ
ﺪﻳدﺮﮔ مﺎﺠﻧا ،ﺪﻧدﻮﺑ ﻪﺘﻓﺮﮔ .
داﺮﻓا
ﺖﺑﺎﻳد ﻪﺑ نﺎﻳﻼﺘﺒﻣ ،HIV+
ﻣ و
هﺪـﻨﻨﻛ فﺮﺼ
يﺎـﻫ زا يﺪﻴﺋوﺮﺘـﺳاﻮﻜﻴﺗرﻮﻛ يﺎـﻫوراد
ﺪﻧﺪﺷ فﺬﺣ ﻪﻌﻟﺎﻄﻣ درﻮﻣ ﺖﻴﻌﻤﺟ .
ﻲـﻧاﺮﻳا نارﺎـﻤﻴﺑ ﻲﻣﺎﻤﺗ
ــﺤﻣ رد و ﺪــﻧدﻮﺑ ﺪ
ﻲﻨــﺳ هدو
±35 51 لﺎــﺳ ﺪﻨﺘــﺷاد راﺮــﻗ .
3 / 58 و نادﺮـﻣ ار داﺮﻓا ﻦﻳا ﺪﺻرد 7
/ 41 ار ﺎـﻬﻧآ ﺪـﺻ رد
ﻞﻴﻜﺸﺗ نﺎﻧز ﻲﻣ
ﺪﻧداد .
ﻪﻧﻮﻤﻧ ﻲﻳوراد ﺖﻣوﺎﻘﻣ ﺮﻈﻧ زا
يﺎـﻫ
ارﺎﻤﻴﺑ زا هﺪﺷ اﺪﺟ رد ،ن
5 / 86 % دراﻮﻣ
، وراد ﻪﺑ ﺖﻴﺳﺎﺴﺣ
و ﺖﺷاد دﻮﺟو 5
/ 11 %
ﺪـﻧدﻮﺑ موﺎـﻘﻣ وراد ﻪـﺑ ﺰﻴﻧ .
داﺪـﻌﺗ
122
ﻲﺗﺎﻘﻴﻘﺤﺗ ﺰﻛﺮﻣ ﻪﺑ ﻦﻴﻌﺟاﺮﻣ زا ﺮﻔﻧ -
مﻮـﻠﻋ ﻲـﺷزﻮﻣآ
ﻲﻫﺎﮕﺸﻳﺎﻣزآ )
ناﺮﻳا ﻲﻜﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد (
ﺖﻣﻼﺳ ﻪﻛ ﺰﻴﻧ
ﺗ ﻲﻜﺷﺰﭘ تﺎﻨﻳﺎﻌﻣ ﺎﺑ ﺎﻬﻧآ ﺎ
ﺪﻴﻳ هﺪﺷ هوﺮـﮔ ناﻮـﻨﻋ ﻪـﺑ ،دﻮـﺑ
بﺎﺨﺘﻧا لﺮﺘﻨﻛ ﺪﻧﺪﻳدﺮﮔ
. ﮓﻨﻴﭙﻳﺎﺗﻮﻧژ مﺎﺠﻧا شور
،ﻪــﻌﻟﺎﻄﻣ ﻦــﻳا رد ﻲــﻠﭘ
ﻢﺴــﻴﻓرﻮﻣ يﺎــﻫ
Arg677Trp و
Arg753Gln TLR2رد
ﻦﻴــﻨﭽﻤﻫ و ﻲــﻠﭘ
ﻢﺴــﻴﻓرﻮﻣ يﺎــﻫ
Asp299Gly Thr399Ile و
TLR4رد
، زا هدﺎﻔﺘــــﺳا ﺎــــﺑ
ﻚـــﻴﻨﻜﺗ PCR-SSP
(Polymerase chain reaction
Sequence-Specific Primers) راﺮـــﻗ ﻲـــﺳرﺮﺑ درﻮـــﻣ
ﺪــﻨﺘﻓﺮﮔ . ﺮــﻤﻳاﺮﭘ ﻲــﺣاﺮﻃ يﺎــﻫ
زا هدﺎﻔﺘــﺳا ﺎــﺑ ﺮــﻈﻧ درﻮــﻣ
مﺮــﻧ راﺰــﻓا Primer premier 5.0 ﺖــﻓﺮﮔ ترﻮــﺻ
. ﻪــﻨﻴﻬﺑ
يزﺎــﺳ ﺶﻨــﻛاو ﺰــﻴﻧPCR
ﺎﻣزآ رد ــﻳ ﻮﻤﻳا هﺎﮕﺸ ﻮﻧ
ﻚــﻴﺘﻧژ
ﺖﻓﺮﻳﺬﭘ مﺎﺠﻧا و
ﺎﺑ
ﻲﻟاﻮـﺗ ﻦﻴﻴﻌﺗ (Sequencing)
ﻪـﻓﺮﻃ ود
تﻻﻮﺼﺤﻣ PCR
ﺗ ،هﺪـﺷ ﻲـﺣاﺮﻃ يﺎﻫﺮﻤﻳاﺮﭘ ﺖﺤﺻ ﺎ
ﺪـﻴﻳ
ﺪﻳدﺮﮔ . هرﺎﻤﺷ لوﺪﺟ 1
ﺮﻤﻳاﺮﭘ ﻲﻟاﻮﺗ
يﺎﻫ هدﺎﻔﺘﺳا و هﺪـﺷ
تﻻﻮﺼﺤﻣ هزاﺪﻧا ر
نﺎﺸﻧ ا ﻲﻣ ﺪﻫد .
ﺶﻨـﻛاو ﻲﻣﺎـﻤﺗ رد
ﺎـﻫ
ﻪﻌﻄﻗ يا نژ مﻮﺳ نوﺮﺘﻨﻳا زا HLA-DRB1
لﻮـﻃ ﻪﺑ 796
راﺮـﻗ هدﺎﻔﺘـﺳا درﻮـﻣ ﻲـﻠﺧاد لﺮـﺘﻨﻛ ناﻮـﻨﻋ ﻪـﺑ زﺎﺑ ﺖﻔﺟ ﺖﻓﺮﮔ . ﺺﻴـﻠﺨﺗ رﻮـﻈﻨﻣ ﻪﺑ و نارﺎـﻤﻴﺑ زا ماﺪـﻛ ﺮـﻫ زا ،DNA
لﺮﺘﻨﻛ هوﺮﮔ داﺮﻓا 3
دﺎـﻘﻌﻧا ﺪـﺿ يور ﺮـﺑ نﻮﺧ ﺮﺘﻴﻟ ﻲﻠﻴﻣ
ﺮﮔ EDTA و ﺪﺷ ﻪﺘﻓ DNA
لﻮﺒﻠﮔ زا ﺮﻈﻧ درﻮﻣ
يﺎﻫ ﺪﻴﻔﺳ
شور ﺎـﺑ و ﻲـﻄﻴﺤﻣ نﻮﺧ Salting-out
ﺪـﻳدﺮﮔ جاﺮﺨﺘـﺳا .
ﺶﻨــﻛاو
ﻲــﻠﻛ ﻢــﺠﺣ رد PCR
15 ﻂﻴــﺤﻣ رد و ﺮــﺘﻴﻟوﺮﻜﻴﻣ
ﺪﺷ مﺎﺠﻧا مﻮﻴﻧﻮﻣآ تﺎﻔﻟﻮﺳ يﺮﻓﺎﺑ .
ماﺪﻛ ﺮﻫ ﻲﺳرﺮﺑ ياﺮﺑ
زا ﻲﻠﭘ ﻢﺴﻴﻓرﻮﻣ
يﺎـﻫ ﺎـﺑ ﻪـﻧﺎﮔاﺪﺟ ﺶﻨـﻛاو ود هﺪـﺷ ﺮـﻛذ
مﺎﺠﻧا ﺮﻳز ﻲﺘﻈﻠﻏ ﻂﻳﺮﺷ ﺪﻳدﺮﮔ
.
راﺪــﻘﻣ ﺶﻨــﻛاو ﺮــﻫ رد DNA
50-100ng dNTPs
200µM;
MgCl2 1.5mM;
، يﺎﻫﺮﻤﻳاﺮﭘ زا ماﺪﻛ ﺮﻫ ﺖﻈﻠﻏ
ﻲﺻﺎﺼﺘﺧا 0.5-2 µM
، لﺮـﺘﻨﻛ ﺮـﻤﻳاﺮﭘ ﺖـﻈﻠﻏ 0.1µM
و
ﻢﻳﺰﻧآ ﺖﻈﻠﻏ Taq DNA polymerase
0.5 ﺪﺣاو .
هﺮــﻴﺠﻧز ﺶﻨــﻛاو يا
هﺎﮕﺘــﺳد زا هدﺎﻔﺘــﺳا ﺎــﺑ زاﺮــﻤﻴﻠﭘ
Eppendorf (Mastercycler)
ﺎــﻣﺰﻤﻫ رﻮــﻃ ﻪــﺑ و ياﺮــﺑ ن
ﻲﻣﺎﻤﺗ ﻲﻠﭘ ﻢﺴﻴﻓرﻮﻣ
ﺎﻫ و
ﻲﻳﺎـﻣد ﻂﻳاﺮـﺷ ﺖـﺤﺗ
ﻲﻧﺎـﻣز و
نﺎﺴﻜﻳ ﺮﻳز ﺐﻴﺗﺮﺗ ﻪﺑ مﺎﺠﻧا
ﺪﺷ .
ﻞﻜﺷ هرﺎﻤـﺷ 1
- ﮓـﻨﻴﭙﻳﺎﺗﻮﻧژ يﻮـﮕﻟا و TLR2
ﻚـﻴﻨﻜﺗ زا هدﺎﻔﺘـﺳا ﺎـﺑ TLR4 PCR-SSP
. درﻮـﻣ رد دﺮـﻓ ﻦـﻳا ﭗـﻳﺎﺗﻮﻧژ :TLR2
677Arg/Arg و
753Arg/Arg درﻮﻣ رد و
:TLR4 299Asp/Gly 399Thr/Ile و
ﻲﻣ ﺑ ﺪﺷﺎ .
هرﺎﻤﺷ لوﺪﺟ 1
- ﮓﻨﻴﭙﻳﺎﺗﻮﻧژ رد هﺪﺷ هدﺎﻔﺘﺳا يﺎﻫﺮﻤﻳاﺮﭘ ﻲﻠﭘ
ﻢﺴﻴﻓرﻮﻣ يﺎﻫ ﻲﻜﻴﺘﻧژ TLR2
TLR4 و تﻻﻮﺼﺤﻣ هزاﺪﻧا و PCR
Size (bp) Primers
5'- TCAAGTTGTGTCCTCATAAGC-3' F
Arg
5'- TCAAGTTGTGTCCTCATAAGT-3' F'
677 190
5'- ATGGCAGCATCATTGTTCTC-3' R
Trp F 5'- TCTTGGTGTTCATTATCTTCC-3' Arg
5'- TCTTGGTGTTCATTATCTTCT-3' F'
753 125
5'- CTTCTCCCATTTCCGTCTT-3' R
Gln TLR2
5'- TTAGACTACTACCCCGATGA-3' F
Asp F' 5'- TTAGACTACTACCCCGATGG-3'
299 307
5'- CACTTTGAGAACAGCAACC-3' R
Gln
5'- CAAAGTGATTTCGGGACAAC-3' F
Thr F' 5'-CAAAGTGATTTCGGGACAAT-3'
399 284
5'-ACTTCGAGACTGGACAAGC-3' R
Ile TLR4
5'-TGCCAAGTGGAGCACCCAA-3'
F 5'-GCATCTTGCTCTGTGCAGAT-3' 796 HLA-DRB1 R
(Internal control)
ﺢﻴﺿﻮﺗ : ﻲﻨﻳﺰﮕﻳﺎﺟ ﻚﻳ ﺎﻫﺮﻤﻳاﺮﭘ زا ﻲﺧﺮﺑ ﻲﻳآرﺎﻛ ﺶﻳاﺰﻓا رﻮﻈﻨﻣ ﻪﺑ ﻪﺑ T
ﻪـﻛ هﺪـﻳدﺮﮔ لﺎﻤﻋا C
ﺖﺳا هﺪﺷ هداد نﺎﺸﻧ ﮓﻧرﺮﭘ ترﻮﺻ ﻪﺑ رﻮﻛﺬﻣ ﺪﻴﺗﻮﺌﻠﻛﻮﻧ Mismatched Primers)
.(
2 رد ﻪﻘﻴﻗد 94°C
هﺮـﻴﺠﻧز ﻪـﻴﻟوا نﺪﺷ زﺎﺑ ياﺮﺑ
يﺎـﻫ
،DNA 10 ﻞﻜﻴﺳ 10 ﻪـﻴﻧﺎﺛ يا
°Cرد 94 و 1 ﻪـﻘﻴﻗد يا رد
65°C ؛ 20 ﻞﻜﻴـﺳ 10 ﻪــﻴﻧﺎﺛ يا
°C رد 94
، 50 ﻪــﻴﻧﺎﺛ يا رد
61°C و 30 ﻪﻴﻧﺎﺛ يا
°C رد 72 .
ﺪﻌﺑ مﺎﺠﻧا زا
زرﺎـﮔآ لژ رد ﺶﻨـﻛاو تﻻﻮﺼﺤﻣ PCR
5 / 1 ،يرادﺮﺒﺴــﻜﻋ زا ﺲــﭘ و ﺪــﺷ زرﻮــﻓوﺮﺘﻜﻟا ﺪــﺻرد
ﺺﺨﺸﻣ داﺮﻓا ﭗﻳﺎﺗﻮﻧژ ﺪﻳدﺮﮔ
) ﻞﻜﺷ هرﺎﻤﺷ 1 .(
يرﺎﻣآ ﺰﻴﻟﺎﻧآ
ﺎــﻋﻼﻃا ﻲﻣﺎــﻤﺗ ،ﮓــﻨﻴﭙﻳﺎﺗﻮﻧژ مﺎــﺠﻧا زا ﺲــﭘ ﻂــﺳﻮﺗ ت
مﺮﻧ راﺰﻓا SPSS v.11
ﺖـﻓﺮﮔ راﺮـﻗ ﻞـﻴﻠﺤﺗ و ﻪﻳﺰﺠﺗ درﻮﻣ .
ﻲﭙﻳﺎـــﺗﻮﻧژ و ﻲـــﻠﻟآ ﻲـــﻧاواﺮﻓ ،ﻲﻔﻴـــﺻﻮﺗ يﺎـــﻫﺰﻴﻟﺎﻧآ رد ﻲﻠﭘ ﻢﺴﻴﻓرﻮﻣ يﺎﻫ
TLR2 نژ TLR4 و
هوﺮﮔ رد يﺎﻫ
ﺪﻫﺎﺷ
ﺪــﻳدﺮﮔ ﺺﺨﺸــﻣ رﺎــﻤﻴﺑ و )
هرﺎﻤــﺷ لوﺪــﺟ 2
.(
ﺰﻴﻟﺎــﻧآ رد
ﻖـﻴﻗد نﻮـﻣزآ و نﻮـﺳﺮﻴﭘ ﺮﺋﻮﻜﺳا يﺎﻛ نﻮﻣزآ زا ﻲﻠﻴﻠﺤﺗ
ﺳرﺮﺑ ياﺮﺑ ﺮﺸﻴﻓ
ﻦﻴـﺑ طﺎـﺒﺗرا دﻮـﺟو مﺪـﻋ ﺎﻳ و دﻮﺟو ﻲ
ﻲــﻠﭘ ﻢﺴــﻴﻓرﻮﻣ نژ يﺎــﻫ
و TLR2
ﻞــﺳ يرﺎــﻤﻴﺑ و TLR4
ﺪﺷ هدﺎﻔﺘﺳا .
ﻪﺘﻓﺎﻳ ﺎﻫ ﻲﻠﭘ درﻮﻣ رد ﻢﺴـﻴﻓرﻮﻣ
يﺎـﻫ ﻞـﻟآ ،TLR2
677Trp رد
هرﺎﻤﺷ لوﺪﺟ 2
- ﻲﻠﭘ ﻲﭙﻳﺎﺗﻮﻧژ و ﻲﻠﻟآ ﻲﻧاواﺮﻓ ﻢﺴﻴﻓرﻮﻣ
يﺎﻫ TLR2 نژ TLR4 و هوﺮﮔ رد يﺎﻫ لﺮﺘﻨﻛ و رﺎﻤﻴﺑ .
Thr399Ile Asp299Gly
Arg753Gln Arg677Trp
Allele%
Genotype%
Allele%
Genotype%
Allele%
Genotype%
Allele%
Genotype%
I T II TI TT G D GG DG DD Q R QQ RQ RR W R WW RW RR
2 /
4 *
8 / 0 95 3 / 8 7 / 91 3 / 7 * 7 / 0 92 6 / 14 4 / 0 83 100 0 0 100 0 100 0 0 100 Patients
8 / 0 2 / 99 0 6 / 1 4 / 98 9 / 2 1 / 97 0 8 / 5 2 / 94 8 / 0 2 / 99 0 6 / 1 4 / 98 0 100 0 0 Controls 100
هوﺮﮔ زا ماﺪﻛ ﭻﻴﻫ يﺎﻫ
ﺪـﻳدﺮﮕﻧ هﺪﻫﺎﺸﻣ رﺎﻤﻴﺑ و ﺪﻫﺎﺷ .
ﻞــﻟآ ﻲــﻧاواﺮﻓ 753Gln
ﺪﻫﺎــﺷ هوﺮــﮔ رد 8
/ 0 % رد و دﻮــﺑ
ﺖــﺷاﺪﻧ دﻮــﺟو ﻞــﺳ ﻪــﺑ ﻼﺘــﺒﻣ ﺖــﻴﻌﻤﺟ .
ﺎــﺑ ﻪــﻄﺑار رد
ﻲــﻠﭘ ﻢﺴــﻴﻓرﻮﻣ يﺎــﻫ
ﻲــﻨﻌﻣ طﺎــﺒﺗرا ﻪــﻛ TLR4 ﺎــﺑ يراد
ﻞــﻟآ ﻲــﻧاواﺮﻓ ،ﺪﻨﺘــﺷاد يﻮــﻳر ﻞــﺳ يرﺎــﻤﻴﺑ 299G
رد
هوﺮﮔ يﺎﻫ
ـﻴﺗﺮﺗ ﻪـﺑ ﺪﻫﺎـﺷ و رﺎـﻤﻴﺑ ﺐ
3 / 7 % و 9 / 2 % دﻮـﺑ
) 028 / P value =0 ،
73 / 6 - 1 / 1 CI ؛ 95
% ، 66 / OR=2 ( و
ﻲـﻠﻟآ ﻲﻧاواﺮﻓ نارﺎـﻤﻴﺑ رد 399I
8 / 0 % هوﺮـﮔ داﺮـﻓا رد و
ﺪﻫﺎﺷ 2 / 4 % دﻮـﺑ ) 022 / 0 P value = ،
1 / 25 - 1 / 1 CI ؛ 95
% ،
26 / 5 OR = .(
هوﺮـﮔ زا ماﺪﻛ ﭻﻴﻫ رد ،هﺪـﺷ ﻲـﺳرﺮﺑ يﺎـﻫ
ﺖﺷاﺪﻧ دﻮﺟو ﻪﺘﻓﺎﻳ ﺶﻬﺟ ﻞﻟآ تﻮﮕﻳزﻮﻤﻫ ﺖﻟﺎﺣ .
ﺤﺑ ﺚ
شﻮـﻣ ﻪﻛ ﺪﻧا هداد نﺎﺸﻧ ﻲﻧاﻮﻴﺣ تﺎﻌﻟﺎﻄﻣ
ﺎـﻫ ﺪـﻗﺎﻓ ي
TLR2 نژ زا ﻲـــﺷﺎﻧ ﻲﻤـــﺳ ﻲﺘﭙـــﺳ ﺪﻌﺘﺴـــﻣ ، ﻲـــﺧﺮﺑ
يﺮﺘﻛﺎــﺑ ﺖــﺒﺜﻣ مﺮــﮔ يﺎــﻫ
ﺎــﺑ ﺖــﻧﻮﻔﻋ و مﻮﻳﺮﺘﻛﺎــﺑﻮﻜﻳﺎﻣ
ﻲﻣ ﺪﻨﺷﺎﺑ
).
10 و 11
(
ﺮﻈﻧ ﻪﺑ ﻲﻣ ﻪـﻛ ﺪﺳر ﻲـﻠﭘ
ﻢﺴـﻴﻓرﻮﻣ
ﺎـﻫ ي
ﻲﻜﻴﺘﻧژ ﺰﻴﻧ TLR2
دﺮﻜﻠﻤﻋ رد ﻪﻛ لﻮﻜﻟﻮﻣ
دﺎـﺠﻳا لﻼﺘـﺧا
ﻲﻣ ﺪﻨﻨﻛ ﻢﻫ
ﺳﺎﭘ رد ﺺﻘﻧ ﻪﺑ ﺮﺠﻨﻣ ﻒـﻴﻃ ﻪﺑ ﻲﺗاذ ﻲﻨﻤﻳا ﺦ
نژﻮﺗﺎــــﭘ زا ﻲﺼــــﺨﺸﻣ يﺎــــﻫ
ﺮﻜﻴﻣ و ﺪــــﻧدﺮﮔ ﻲــــﺑ .
ﻲــﻠﭘ ﻢﺴــﻴﻓرﻮﻣ يﺪــﻴﺗﻮﺌﻠﻛﻮﻧ ﻚــﺗ يﺎــﻫ
Arg677Trp و
Arg753Gln ﻣود رد
ﻴ TIR ﻦ لﻮﻜﻟﻮﻣ دﺎﺠﻳا ﺮﻴﻴﻐﺗ TLR2
و هدﺮﻛ
ﻣ ار مﺎﻴﭘ لﺎﻘﺘﻧا ﻞﻤﻋ ﻞﺘﺨ
ﻲﻣ ﺪﻨﻳﺎﻤﻧ
).
12
ﻪـﺟﻮﺗ ﺎﺑ (
ﻪﺘﺷﺬﮔ تﺎﻌﻟﺎﻄﻣ ﻪﺑ ﺮﻈﻧ ﻪﺑ
ﻲـﻣ ﻪـﻛ ﺪـﺳر ﻲـﻠﭘ
ﻢﺴـﻴﻓرﻮﻣ
Arg677Trp ﺗ
ﺖــﻴﻌﻤﺟ رد ﺎــﻬﻨ ﺎــﻫ
ي آ يﺎﻴــﺳآ و ﻲﻳﺎــﻘﻳﺮﻓ
ﻲﻗﺮﺷ ﺖـﻓﺎﻳ ﺖـﺳﻮﭘﺪﻴﻔﺳ داﮋـﻧ رد و ﺪﺷﺎﺑ ﻪﺘﺷاد دﻮﺟو
ﺖﺳا هﺪﺸﻧ
).
13
ﻂﻳاﺮـﺷ رد (
In vitro ﻦـﻳا ،
ﻲـﻠﭘ ﻢﺴـﻴﻓرﻮﻣ ﺖــﻴﻟﺎﻌﻓ
و هﺮــﭙﻟ مﻮﻳﺮﺘﻛﺎــﺑﻮﻜﻳﺎﻣ ﻪــﺑ ﺦــﺳﺎﭘ رد ار NFκB
رﺎﻬﻣ ،ﺲﻳزﻮﻟﻮﻛﺮﺑﻮﺗ مﻮﻳﺮﺘﻛﺎﺑﻮﻜﻳﺎﻣ ﻲﻣ
ﺪﻨﻛ يداﺮـﻓارد و
ﺶﻬﺟ ﻦﻳا ﻞﻣﺎﺣ ﻪﻛ ﻲﻣ
ﭘ ﺢﻄﺳ ،ﺪﻨﺷﺎﺑ IL-12 ﻪﻳﺎ
ﺢﻄـﺳ و
ﺎﺑ ﻚﻳﺮﺤﺗ زا ﺲﭘ ﻦﻳﺎﻛﻮﺘﻳﺎﺳ ﻦﻳا ﺶﻫﺎـﻛ مﻮﻳﺮﺘﻛﺎـﺑﻮﻜﻳﺎﻣ
دراد
).
14 و 15
IL-12(
ﺮﻴﺴـﻣ يﺎـﻘﻟا ﺐﺟﻮﻣ
IFN-γ دﺎـﺠﻳا و
ﺦﺳﺎﭘ TH1
ﻪﻛ ﻪﺘﺸﮔ ﻲﻣ
ﻲﻨﻴﻟﺎﺑ طﺎﺒﺗرا هﺪﻨﻨﻛ ﻪﻴﺟﻮﺗ ﺪﻧاﻮﺗ
ﻦﻳا ﻲﻠﭘ ﻢﺴﻴﻓرﻮﻣ
يرﺎـﻤﻴﺑ ﺎﺑ ﺎـﻫ
ـﻳﺮﺘﻛﺎﺑﻮﻜﻳﺎﻣ ي لﺎ
) ماﺬـﺟ
ﻮـﺗ رد يﻮـﻳر ﻞﺳ و هﺮﻛ رد زﻮﺗﺎﻣوﺮﭙﻟ ﺲﻧ
ﺪـﺷﺎﺑ
).
16 و 17 (
ﻦﻳا ﻲﻠﭘ ﻢﺴﻴﻓرﻮﻣ رد
22 % هﺮـﻛ رد ماﺬﺟ ﻪﺑ ﻼﺘﺒﻣ نارﺎﻤﻴﺑ
رد و هدﻮﺑ زﻮﺗﺎﻣوﺮﭙﻟ ماﺬﺟ ﻪﺑ طﻮﺑﺮﻣ ﻂﻘﻓ ﻪﻛ هﺪﺷ هﺪﻳد ماﺬـﺟ ﻪـﺑ ﻼﺘـﺒﻣ داﺮـﻓا و لﺮـﺘﻨﻛ هوﺮﮔ داﺮﻓا زا ماﺪﻛ ﭻﻴﻫ ﺪﻴﺋﻮﻟﻮﻛﺮﺑﻮﺗ )
ﻞﻴـﺳﺎﺑ ﻢـﻛ ناﺰـﻴﻣ ﺎـﺑ ﻪﻛ يرﺎﻤﻴﺑ زا ﻲﻣﺮﻓ
ﺖﺳا هاﺮﻤﻫ (
ﺖﺳا هﺪﺸﻧ ﺖﻓﺎﻳ ،
).
16
درﻮﻣ رد (
ﻲﻠﭘ ﻓرﻮﻣ ﻢﺴﻴ
Arg753Gln
ﻚﻴﺘﭙﺳ كﻮﺷ ﺎﺑ نآ طﺎﺒﺗرا ﻪﻌﻟﺎﻄﻣ ﻚﻳ رد ،
يﺮﺘﻛﺎﺑ رد ﺰﻴﻧ نآ ﻲﻧاواﺮﻓ و هﺪﺷ شراﺰﮔ ﺖﺒﺜﻣ مﺮﮔ يﺎﻫ
نﺎﺘﺳﻮﭘ ﺪﻴﻔﺳ 7
/ 2 % ﺖﺳا هدﻮﺑ
).
18
(
قﺎﺸﻨﺘﺳا زا ﺲﭘ ﻪﻛ هﺪﺷ هداد نﺎﺸﻧ يدﺎﻳز تﺎﻌﻟﺎﻄﻣ رد LPS
ﻲﻣ ﻢﺳآ ﻪﻴﺒﺷ ﻲﺘﻟﺎﺣ رﺎﭼد صﺎﺨﺷا
ﺪﻧدﺮﮔ . ﺖـﻟﺎﺣ ﻦﻳا
ا زا ﺮﺗﺪﻳﺪﺷ ﻚﻳژﺮﻟآ داﺮﻓا رد ﻦﻴـﻋ رد ﺎـﻣا هدﻮـﺑ ﻲﻌﻴﺒﻃ داﺮﻓ
قﺎﺸﻨﺘﺳا ﺎﺑ ﺰﻴﻧ داﺮﻓا ﻲﺧﺮﺑ لﺎﺣ
ﻲـﺑﺮﺠﺗ ترﻮـﺻ ﻪـﺑ LPS
ﻲﻤﻧ نﺎﺸﻧ دﻮﺧ زا ﻲﺨﺳﺎﭘ ﭻﻴﻫ
ﺪﻨﻫد
).
19
نژ رد(
داﺮـﻓاTLR4
ﻪــﺑ ﺦــﺳﺎﭘ ﻲــﺑ ،LPS
ﻲــﻠﭘ ود ﻢﺴــﻴﻓرﻮﻣ Asp299Gly
و
Thr399Ile هﺪــﻳد ﺮﺘﺸــﻴﺑ
هﺪــﺷ ﺪــﻧا
).
19 و 20
ﻪــﻛ ﻦــﻳا ﻞــﻴﻟد ﻪــﺑ (
SNP
يﺎﻫ
ﺪـﻨﻨﻛ ﻲﻳﺎـﺳﺎﻨﺷ ﻪـﻴﺣﺎﻧ رد قﻮﻓ لﻮـﻜﻟﻮﻣ ه
TLR4
ﻲﻣ رﺎﻈﺘﻧا ﻦﻳاﺮﺑﺎﻨﺑ ،ﺪﻧراد راﺮﻗ
ﺪـﻧﺎﮕﻴﻟ ﻲﻳﺎﺳﺎﻨﺷ ﻞﻤﻋ ﻪﻛ دور
ﻞﻟآ رد
دﺮـﻴﮕﻧ ترﻮـﺻ ﻲﺑﻮﺧ ﻪﺑ ﻪﺘﻓﺎﻳ ﺶﻬﺟ يﺎﻫ .
زا ﻲـﺧﺮﺑ
ﻦﻳا ﺮﻴﺛﺎﺗ ﺰﻴﻧ ﺮﮕﻳد تﺎﻌﻟﺎﻄﻣ ﻪـﺑ ﻼﺘـﺑا داﺪﻌﺘـﺳا ﺮﺑ ار ﺎﻫSNP
ﺖﻧﻮﻔﻋ ﺪﻨﻧﺎﻣ ﺎﻫ
يﺮﺘﻛﺎﺑ ﺎﺑ ﺖﻧﻮﻔﻋ ﻲﻃ ﻚﻴﺘﭙﺳ كﻮﺷ
ﺎﻫ مﺮﮔ ي
تﺪﺷ ،ﻲﺣاﺮﺟ زا ﺲﭘ ﺲﻴﺴﭙﺳ ،ﻲﻔﻨﻣ ﻲﺑﺎـﻬﺘﻟا ﺦﺳﺎﭘ مرﺪﻨﺳ
ﻢﻧﺎﺧ لﺎﻨﻳژاو نﻮﻴﺳاﺰﻴﻧﻮﻠﻛ ،دﺎﺣ
يﺎﻫ
يﺮﺘﻛﺎـﺑ ﺎﺑ رادرﺎﺑ
يﺎـﻫ
زا ﻲــﺷﺎﻧ دﺎــﺣ ﺖﻴﺸــﻧوﺮﺑ ،لﺎﺴــﻨﻣﻮﻛ نادازﻮــﻧ رد RSV
،
يرﺎﻤﻴﺑ يﺎﻫ ﻲﻜﻛﻮﮕﻨﻨﻣ
و ﻂـﺳﻮﺘﻣ ﻦﻣﺰﻣ ﺖﻴﺘﻧدﻮﻳﺮﭘ ، و دﺎـﺣ
سﻮـﭘﻮﻟ و ﺪـﻴﺋﻮﺗﺎﻣور ﺖﻳﺮﺗرآ ﺪـﻧداد راﺮـﻗ ﻲﺑﺎـﻳزرا درﻮـﻣ
ﺎــﺒﺗرا ﻦﺘﻓﺎــﻳ ﻪــﺑ ﻖــﻓﻮﻣ ﺎــﻬﻧآ زا ﻲــﺧﺮﺑ ﻪــﻛ ﻦﻴــﺑ ط
SNP
ﺮﻈﻧ درﻮﻣ
ﺖـﻧﻮﻔﻋ ﻪـﺑ ﻼﺘـﺑا داﺪﻌﺘـﺳا ﺶﻳاﺰـﻓا و
قﻮـﻓ يﺎـﻫ
هﺪﻳدﺮﮔ ﺪﻧا
).
30 - 21
(
ﻚـﻳ ﻪﺑ ﻼﺘﺑا داﺪﻌﺘﺳا ﻦﻴﻴﻌﺗ رد ﺎﻬﻨﺗ ﻪﻧ ﻲﻜﻴﺘﻧژ تﺎﻌﻟﺎﻄﻣ
ﻪـﻜﻠﺑ ﺪﻨﺘﺴـﻫ ﺖـﻴﻤﻫا ﺰﺋﺎـﺣ صﺎـﺧ يرﺎﻤﻴﺑ
ﻲـﻣ رد ﺪـﻨﻧاﻮﺗ
رﺎﻴﺴـﺑ ﺰـﻴﻧ يرﺎـﻤﻴﺑ ﺰﻧژﻮﺗﺎـﭘ و يژﻮﻟﻮﻴﺑ نﺪﺷ ﺮﺗ ﻦﺷور
ﺪﻨـﺷﺎﺑ هﺪـﻨﻨﻛ ﻚـﻤﻛو ﺪﻨﻣدﻮﺳ .
ﻲﻫﺎـﮔآ ﻦـﻳا زا ﺎـﻣ ﺮﺘﺸـﻴﺑ
ﻢﺴﻴﻧﺎﻜﻣ
يرﺎﻤﻴﺑ درﻮﻣ رد ﺎﻫ ﺎﻫ
ـﺘﻳﺎﻬﻧ ﻲﻧﻮﻔﻋ ي
ًﺎ ﻲـﻣ ﺪـﻧاﻮﺗ
ﺪـﻳﺪﺟ ﻲﻧﺎـﻣرد يﺎـﻫرﺎﻜﻫار يﺮـﻴﮔ ﻞﻜـﺷ ﻪﺑ ﺮﺠﻨﻣ )
ﺪـﻨﻧﺎﻣ
يﺎﻫﺪــﻧﺎﮕﻴﻟ زا هدﺎﻔﺘــﺳا و ﻲﭘاﺮﺗﻮــﻧﻮﻤﻳا
ﺎــﻫTLR ( ﺖﺧﺎــﺳ ،
ﻦﺴﻛاو ﺎﻫ
شور دﺮﺒﺸﻴﭘ و ﺮﺗﺮﺛﺆﻣ ي ﺎﻫ
ﻚﻴﻣﻮﻧژﻮﻛﺎﻣرﺎﻓ ي
يرﺎــﻤﻴﺑ لﺎــﻌﻓ مﺮــﻓ ﻪــﺑ ﺖــﻧﻮﻔﻋ ﺖﻓﺮﺸــﻴﭘ زا و هﺪــﻳدﺮﮔ ﺪﻨﻛ يﺮﻴﮔﻮﻠﺟ .
ﻪﺠﻴﺘﻧ يﺮﻴﮔ
ﻲﻣ نﺎﺸﻧ ﻪﻌﻟﺎﻄﻣ ﻦﻳا رد هﺪﻣآ ﺖﺳد ﻪﺑ ﺞﻳﺎﺘﻧ ﻪـﻛ ﺪـﻨﻫد
ﻲﻠﭘ ﻢﺴﻴﻓرﻮﻣ
لﻮﻜﻟﻮﻣ ﻲﻜﻴﺘﻧژ يﺎﻫ
) TLR4
Asp299Gly و
Thr399Ile (
ﺘﺑا داﺪﻌﺘﺳا ﺮﺑ ﺖﺳا ﻦﻜﻤﻣ رد يﻮﻳر ﻞﺳ ﻪﺑ ﻼ
ﺎﺗ ﻲﻧاﺮﻳا ﺖﻴﻌﻤﺟ ﻪـﻛ ﺖـﺳا ﻲﻟﺎﺣ رد ﻦﻳا و ﺪﻨﺷﺎﺑ راﺬﮔ ﺮﻴﺛ
ﻲﻠﭘ ﻢﺴـﻴﻓرﻮﻣ يﺎـﻫ
Arg677Trp و
Arg753Gln لﻮـﻜﻟﻮﻣ
و ﻪﺘـﺷاد ﻲﻨﻴﻳﺎـﭘ رﺎﻴﺴـﺑ عﻮﻴـﺷ ﻲﻧاﺮﻳا ﺖﻴﻌﻤﺟ رد TLR2
ﺗ ﺎ ﻪـﺑ ﻞـﻤﺘﺤﻣ ﺮـﻴﻏ يﻮﻳر ﻞﺳ ﻪﺑ ﻼﺘﺑا داﺪﻌﺘﺳا ﺮﺑ ﺎﻬﻧآ ﺮﻴﺛ
ﻲﻣ ﺮﻈﻧ ﺪﺳر .
ﻊﺑﺎﻨﻣ ﺖﺳﺮﻬﻓ
1- Delgado JC, Baena A, Thim S, Goldfeld AE.
Ethnic-Specific genetic association with pulmonary tuberculosis. J inf dis. 2002; 186: 1463-680
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3- Underhill DM, Ozinsky A, Smith KD, Aderem A.
Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc Natl Acad Sci. 1999; 96: 14459-463
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422-29
8- Means TK, Lien E, Yoshimura A, Wang S, Golenbock DT, Fenton MJ. The CD14 ligands lipoarabinomannan and lipopolysaccharide differ in their requirement for Toll-like receptors. J Immunol. 1999;
163: 6748-755
9- Hanekom W, Abel B, Scriba T. Immunological protection against tuberculosis. SAMJ. 2007; 97: 973-77
10- Takeuchi O, Hoshino K, Akira S. Cutting edge:
TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J
Immunol. 2000; 165: 5392-396
11- Wetzler L. The role of Toll-like receptor 2 in microbial disease and immunity. Vaccine. 2003; 21: 55-60
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388: 394-97
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Immunology. 2004; 112: 674-80
15- Bochud PY, Hawn TR, Aderem A. Cutting edge:
A Toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediatemycobacterial signaling. J Immunol. 2003; 170:
3451-454
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Association between Toll-like Receptor 4 (TLR4) Genetic Polymorphisms and Susceptibility to Pulmonary Tuberculosis
N.Tajik,PhDI M.R.Nasiri,MScII M.Jafari,MscII
T.Mousavi,PhDIII P.Farnia,PhDIV A.R.Salekmoghaddam,PhDIII M.Sankian,PhDV
Abstract
Background & Aim: Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) are the members of the Toll-like receptor family and play important roles in recognition and subsequent immune response against mycobacteria. Two functional polymorphisms for TLR2 (Arg677Trp, CÆT; Arg753Gln, GÆA) and TLR4 (Asp299Gly, AÆG; Thr399Ile, CÆT) genes have been associated with a negative influence on their function, which may affect the innate host response to mycobacteria. The aim of this study was to investigate TLR2 and TLR4 genetic variants in a sample of Iranian patients with pulmonary tuberculosis compared to healthy controls.
Patients and Method: A case-control study was carried out on 96 patients and 122 ethnically matched healthy controls. Genotyping protocol was based on a novel polymerase chain reaction sequence-specific primers (PCR-SSP) method. Allelic and genotypic distribution of mentioned polymorphisms were compared by using Fischer’s exact test between patient and control groups.
Results: The prevalence of TLR4 variant alleles (Gly299 and Ile399) was significantly higher among patients compared to control individuals (Gly299: 7.2% vs. 2.9%, OR=2.66, P=0.028 and Ile399: 4.2% vs.
0.8%, OR= 5.26, P value = 0.022). Regarding TLR2 Arg753Gln polymorphism, no significant difference was observed between patient and control groups (0% vs.0.8%, P>0.05). The other TLR2 polymorphism (Arg677Trp) was not found in any of the studied subjects.
Conclusion: Our data demonstrates that TLR4 genetic polymorphisms may influence the risk of developing tuberculosis after exposure to mycobacterium. In addition, very low frequency of TLR2 genetic variants is revealed in Iranian population.
Key Words: 1) Tuberculosis 2) Genetic Polymorphism 3)Toll-like Receptors 4) Iranian Population
This article is an abstract of M.R.Nasiri's thesis advised by Dr.Tajik and Dr.Mousavi and read by Dr. Salekmoghddam, Dr. Farnia and Dr. Sankian in partial fulfillment of an MSc degree in immunology.
I) Associate Professor of Immunology, Division of Transplant Immunology and Immunogenetics. Department and Research Center of Immunology.Faculty of Medicine. Iran University of Medical Sciences and Health Services.Tehran,Iran.(*Corresponding Author)
II) MSc in Immunology,. Division of Transplant Immunology and Immunogenetics. Department and Research Center of Immunology.Faculty of Medicine. Iran University of Medical Sciences and Health Services.Tehran,Iran.
III) Professor of Immunology, Division of Transplant Immunology and Immunogenetics. Department and Research Center of Immunology.Faculty of Medicine. Iran University of Medical Sciences and Health Services.Tehran,Iran.
Iv) Assistant Professor of Mycrobiology, Mycobacteriology Research Center. Masih-Daneshvari Hospital.Faculty of Medicine. Shahid Beheshti University of Medical Sciences and Health Services.Tehran,Iran.
v) Assistant Professor of Immunology, Department of Immunology. Faculty of Medicine. Mashhad University of Medical Sciences and Health Services.Mashhad,Iran.
