ÃâÒßѧÂÛÎÄ

Äúµ±Ç°µÄλÖãºÑ§ÊõÌà > ҽѧÂÛÎÄ > »ù´¡Ò½Ñ§ÂÛÎÄ > ÃâÒßѧÂÛÎÄ >

ÒÂÔ­ÌåÒÖÖÆËÞÖ÷µÄÃâÒßÓ¦´ðÓëϸ°ûµòÍö

À´Ô´£ºÏ¸°ûÓë·Ö×ÓÃâÒßѧÔÓÖ¾ ×÷ÕߣººÎ˼ÇÛ
·¢²¼ÓÚ£º2021-06-04 ¹²11158×Ö

¡¡¡¡Õª    Òª£º¡¡È«Çò·¶Î§ÄÚÒÂÔ­Ìå¸ÐȾ²¡Àý²»¶ÏÔö¼Ó£¬ÇÒ³¬¹ý°ëÊý»¼Õß±íÏÖΪ³ÖÐøÐÔ¸ÐȾ»òÎÞÖ¢×´¸ÐȾ£¬Õâ¿ÉÄܹéÒòÓÚÒÂÔ­ÌåµÄÃâÒßÌÓÒÝ»úÖÆ¡£ÓÕ·¢ÒÂÔ­Ìå³ÖÐøÐÔ¸ÐȾµÄÍâ½çÒòËØ°üÀ¨¿¹ÉúËصÄ×÷ÓÃÓ벡¶¾¹²¸ÐȾµÈ£¬Í¬Ê±ÒÂÔ­Ìå¸ÐȾ¿ÉÒÖÖÆÃâÒßϸ°ûÓ¦´ð²¢ÒýÆðËÞÖ÷ϸ°ûµòÍö¶øÓ°ÏìÃâÒßϸ°ûµÄ¹¦ÄÜ£¬Èç´Ù½ø¾ÞÊÉϸ°ûµÄ¼«»¯¡¢ÒÖÖÆÖÐÐÔÁ£Ï¸°ûɱ¾ú×÷ÓᢴٽøTϸ°ûµÄºÄ½ßµÈ¡£ÉîÈëÑо¿ÒÂÔ­Ìå¸ÐȾµÄÃâÒßѧ»úÖÆ¿ÉΪδÀ´µÄÒßÃçÑз¢Ìṩ²Î¿¼¡£

¡¡¡¡¹Ø¼ü´Ê£º¡¡ÒÂÔ­Ìå; ÃâÒßÌÓÒÝ; ³ÖÐøÐÔ¸ÐȾ; ÃâÒßÓ¦´ð; ×ÛÊö;

¡¡¡¡ÒÂÔ­Ìå(Chlamydia)ÊÇÒ»ÖÖרÐÔ°ûÄÚ¼ÄÉú¾ú£¬ ÄÜÒýÆðÈËÓ붯ÎïµÄ¶àÖÖ¼²²¡¡£³£¼ûµÄÁÙ´²ÀàÐÍÓУº ɳÑÛÒÂÔ­Ìå(C. trachomatis)ÊÇ×îÖ÷ÒªµÄÐÔ´«²¥¼²²¡µÄ²¡Ô­¾ú£¬ ´æÔÚ¶àÖÖÉúÎïÐÍ£¬ ¿ÉÒýÆðɳÑÛ£¬ ÑÏÖØÕßÖÂ䣬 Ò²¿ÉÔì³ÉÃÚÄòÉúÖ³µÀºÍ¸ØÃÅÖ±³¦¸ÐȾ£¬ Òà¿Éµ¼ÖÂÐÂÉú¶ù·ÎÑ×[1]¡£ðÐðÄÈÈÒÂÔ­Ìå(C. psittaci)ΪÈËÊÞ¹²»¼²¡Ô­Ì壬 ´«È¾ÐÔÓëÖ²¡Á¦Ç¿£¬ ³£ÒýÆðÈ«ÉíÐÔ¼²²¡[2]¡£·ÎÑ×ÒÂÔ­Ìå(C. pneumoniae)³£ÒýÆðºôÎüµÀÖ¢×´£¬ ¿É×Ô·¢ÏûÍËÒà¿É·¢Õ¹Îª·ÇµäÐÍ·ÎÑ×£¬ Óë°üÀ¨¶¯ÂöÖàÑùÓ²»¯ºÍÏø´­ÔÚÄڵĶàÖÖÂýÐÔ¼²²¡Ïà¹Ø[3]¡£´ËÍ⣬ ¶¯ÎïÖ²¡ÐÔÒÂÔ­Ìå°üÀ¨ÊÞÀàÒÂÔ­Ìå(C. pecorum)¡¢ ÊóÒÂÔ­Ìå(C. muridarum)¡¢ ëàÊóÒÂÔ­Ìå(C. caviae)¡¢ ÖíÒÂÔ­Ìå(C. suis)¡¢ Á÷²úÒÂÔ­Ìå(C. abortus)µÈ¡£ÖÚ¶àµÄÒÂÔ­Ìå¸ÐȾͨ³£±íÏÖΪ³ÖÐøÐÔ¸ÐȾ¡¢ ÎÞÖ¢×´¸ÐȾ»ò·´¸´¸ÐȾ£¬ µ¼ÖÂÒÂÔ­Ìå¼²²¡µÄÁ÷Ðкʹ«²¥Ôö¼Ó¡£¶øËÞÖ÷¿¹ÒÂÔ­ÌåµÄ±£»¤Á¦Èõ£¬ Ä¿Ç°Ò²ÉÐÎÞÓÐЧÒßÃ磬 ÐèÒª½øÒ»²½Ñо¿ËÞÖ÷¶Ô¸Ã²¡Ô­ÌåµÄÃâÒßÓ¦´ð£¬ ΪÒÂÔ­ÌåµÄÖ²¡»úÖÆÑо¿¼°Æä·ÀÖÎÌṩÀíÂÛÒÀ¾Ý¡£ÒÔÏÂÖ÷ҪΧÈÆËÞÖ÷ÃâÒßϸ°ûÓ¦´ð£¬ ×ܽáһЩ¹ØÓÚÒÂÔ­ÌåÌÓ±ÜËÞÖ÷ÃâÒßÓ¦´ðµÄÑо¿Ð½øÕ¹¡£

¡¡¡¡1 ¡¢ÒÂÔ­Ìå³ÖÐøÐÔ¸ÐȾ

¡¡¡¡1.1¡¢ ÒÂÔ­ÌåµÄÉúÃüÖÜÆÚÓë³ÖÐøÐÔ¸ÐȾ

¡¡¡¡ÒÂÔ­ÌåÓÐ×ÅÏàͬµÄ·¢ÓýÖÜÆÚ£¬ ¼´´Ó¸ÐȾÐÔÔ­Ìå(elementary body, EB)µ½¸´ÖÆÐÍÍø×´Ìå(reticulate body, RB)µÄת±ä¹ý³Ì¡£¸ÐȾÐÔEBÈëÇÖËÞÖ÷ϸ°ûºó£¬ ÔÚ¼ÄÉú¿ÕÅÝ(°üº­Ìå)ÄÚ·¢ÓýÐγÉRB, ËæºóRBÒÔ¶þ·ÖÁѵķ½Ê½£¬ ¾­Êý´ú¸´ÖÆÐγÉ×Ó´úEB¡£48¡«72 hºó£¬ ËÞÖ÷ϸ°ûĤÆÆÁÑ£¬ ´óÁ¿EBºÍRB±»ÊÍ·Å£¬ ¶øEB½«¼ÌÐø¸ÐȾÁÙ½üϸ°û¿ªÊ¼ÐÂÒ»Âֵķ¢ÓýÖÜÆÚ[4]¡£ÒÂÔ­Ìå³ýÒÔÉÏͬ²½µÄ·¢ÓýÖÜÆÚÍ⣬ ÔÚһЩӦ¼¤Òò×ÓµÄ×÷ÓÃÏÂÐγÉά³ÖÉú´æµÄ·ÇµäÐÍ·¢ÓýÖÜÆÚ¡£1950Ä꣬ WeissµÈ[5]·¢ÏÖÓÃÇàùËØ´¦ÀíµÄÊóÒÂÔ­ÌåÔÚ¸´ÖƵĵڶþ¸öÖÜÆÚÖгöÏÖ²»¶ÏÀ©´óÇÒ²»·ÖÁѵÄÒìÐÍRB (aberrant body, AB)¡£ÕâÖÖÍ£Ö¹·¢Óý¡¢ ³ÖÐøÀ©´óµÄABÊÇÒÂÔ­Ìå³ÖÐøÐÔ¸ÐȾµÄÌØÕ÷£¬ ÇҴ˽׶εÄÒÂÔ­Ìå²»¾ßÓд«È¾ÐÔ£¬ ºÜÄѱ»ËÞÖ÷ÃâÒßϵͳ¼à²â¡£
 

ÒÂÔ­ÌåÒÖÖÆËÞÖ÷µÄÃâÒßÓ¦´ðÓëϸ°ûµòÍö
 

¡¡¡¡¶àÖÖÓ¦¼¤Òò×Ó¿ÉÓÕ·¢ÒÂÔ­ÌåµÄ³ÖÐøÐÔ¸ÐȾ£¬ °üÀ¨Òѱ»ÈËÃÇÊìÖªµÄβÄÚõ£°·À࿹ÉúËØ¡¢ γ¸ÉÈÅËØ(interferon-γ, IFN-γ)¡¢ ÓªÑøÎïÖʵÄȱ·¦¡¢ ÈÈÐÝ¿ËÒÔ¼°Ó벡¶¾¹²¸ÐȾµÈ[6]¡£Ò»ÖÖ°ÐÏò×÷ÓÃÓÚ2-¼×»ù-D-³àÞºÌÇ´¼-4-Á×Ëá(2-methyl-D-erythritol-4-phosphate, MEP);¾¶µÄ¿¹ÉúËØ——Á×ùËØ£¬ Ò²ÄÜÓÕ·¢ABµÄ²úÉú¡£Á×ùËØͨ¹ýÒÖÖÆÀàÒìÎì¶þÏ©ºÏ³ÉËùÐèµÄ¹Ø¼üø1-ÍÑÑõ-D-ľͪÌÇ5-Á×ËỹԭÒ칹ø£¬ ʵÏÖ¶ÔÕý³£ÒÂÔ­Ìå·¢ÓýËù±ØÐèµÄMEP;¾¶µÄÒÖÖÆ¡£ÓÃ2 mmol/LµÄÁ×ùËØ´¦ÀíɳÑÛÒÂÔ­Ìå40 hºó¿É¹Û²ìµ½AB, ÇÒ¸ÐȾÐÔ×Ó´úÃ÷ÏÔ¼õÉÙ[7]¡£´ËÍ⣬ еÄÑо¿·¢ÏÖ£¬ ÒÔÍùÓÃÓÚÒÂÔ­Ìå¸ÐȾÖÎÁƵÄÇ¿Á¦Ã¹ËØ£¬ ÔÚ(0.03¡«0.015)mg/Lʱ¿ÉÓÕµ¼É³ÑÛÒÂÔ­Ìå³ÖÐøÐÔ¸ÐȾ[8]¡£

¡¡¡¡µ±ÒÂÔ­ÌåʧȥÍâ½çÓ¦¼¤Òò×ÓµÄ×÷ÓÃʱ¿É»Ö¸´³ÉÕý³£µÄRBÐÎ̬£¬ ¼ÌÐøÍê³ÉÆä·¢ÓýÖÜÆÚ¡£ÓÐÑо¿·¢ÏÖÒÖÖÆÉ«°±Ëá¡¢ ÁÁ°±ËátRNAºÏ³ÉøµÄßÅßáùËغÍÓÐЧµÄÑ¡ÔñÐÔÁÁ°±õ£-tRNAºÏ³ÉøÒÖÖƼÁAN3365(epetraborole)¼´(S)-3-°±»ù¼×»ù-7-(3-ôÇ»ù-±ûÑõ»ù)-3H-±½²¢[c][1,2]¶ñÅðÍé-1-´¼£¬ ·Ö×Óʽ£º C11H16BNO4, ¿ÉÒÖÖÆÒÂÔ­ÌåÉú³¤£¬ ²¢ÔÚÃâÒßÓ«¹â½á¹ûÖй۲쵽ͬIFN-γ´¦Àí×éÏàËƵÄAB, ½è´Ë¹¹½¨ÁËÒÂÔ­Ìå³ÖÐøÐÔ¸ÐȾģÐÍ¡£È»¶ø£¬ È¥³ýÅàÑø»ùÖеÄßÅßáùËغÍAN3365ºóÒÂÔ­Ìå³É¶ÔÊýÔö³¤£¬ ÇÒÆäÐÎ̬ÔÚ24¡«48 hºó»Ö¸´ÖÁÕý³£[9](ͼ1)¡£

¡¡¡¡ÔÚÒÂÔ­ÌåµÄ³ÖÐøÐÔ¸ÐȾ½×¶Î£¬ Æäͨ¹ýÐγÉABÌÓ±ÜÃâÒß¼à²âÓëÇå³ý£¬ ×è¶ÏÍÌÊÉϸ°ûļ¼¯Ðźţ¬ ÔÚ²»ÀûµÄ¼ÄÉú»·¾³ÖÐÉú´æ£» ²¢´Ì¼¤Ï¸°û²úÉú»îÐÔÑõ(reactive oxygen species, ROS), Ôì³É×éÖ¯ËðÉË[10], Ϊ×ÔÉí´´ÔìÓÐÀûµÄ»·¾³£¬ ×îÖÕʵÏÖÃâÒßÌÓÒÝ¡£

¡¡¡¡Í¼1 ÒÂÔ­ÌåµÄÉúÃüÖÜÆÚ
ͼ1 ÒÂÔ­ÌåµÄÉúÃüÖÜÆÚ

¡¡¡¡E: Ô­Ìå(EB), R: Íø×´Ìå(RB), A: ÒìÐÍRB(AB).

¡¡¡¡1.2¡¢ ÒÂÔ­Ìå³ÖÐøÐÔ¸ÐȾÓë¾ÞÊÉϸ°û¼«»¯

¡¡¡¡¾ÞÊÉϸ°ûÔÚ¶àÖÖÉúÀíºÍ²¡Àí±ä»¯Öз¢»Ó×ÅÖØÒª×÷Ó㬠Æä¿ÉËÜÐԱ仯Âú×ãÁË»úÌåÃâÒß¹¦ÄܶàÑùÐÔµÄÐèÇó¡£Ò»Ð©Ñо¿±íÃ÷ÒÂÔ­ÌåµÄ³ÖÐøÐÔ¸ÐȾÓë¾ÞÊÉϸ°û¼«»¯´æÔÚÒ»¶¨µÄÏà¹ØÐÔ¡£

¡¡¡¡ÖÚËùÖÜÖª£¬ ¾ÞÊÉϸ°ûº¬ÓзḻµÄÍÌÊÉÌåºÍÈÜøÌ壬 ²¡Ô­¾úÄÑÒÔÔÚÆäÖдæ»î¡£È»¶ø£¬ GraceyµÈ[11]ÔÚÍÌÊÉÁËÊóÒÂÔ­ÌåµÄM2Ð;ÞÊÉϸ°ûÖй۲쵽³ÉÊìµÄÒÂÔ­Ìå°üº­Ì塣Ϊ½øÒ»²½Á˽âÒÂÔ­ÌåÔÚ¾ÞÊÉϸ°ûÖеÄÉú´æÓë·±Ö³£¬ Ñо¿ÕßÃǶÔÒÂÔ­Ìå¸ÐȾµÄ¾ÞÊÉϸ°û16S RNA±í´ïˮƽ½øÐÐÁ˼ì²â£¬ ½á¹ûÏÔʾ£º ¸ÐȾ24 hºó£¬ 16S RNAÔÚM2Ð;ÞÊÉϸ°ûÖеıí´ïÏÔ×ÅÔö¼Ó£¬ ¶øÆäÔÚM1Ð;ÞÊÉϸ°ûÖеıí´ï±£³Ö²»±ä[12]¡£´ËÍ⣬ ÓÐÑо¿Õß·¢ÏÖ·ÎÑ×ÒÂÔ­Ìå¸ÐȾ´¥·¢µòÍöÒÖÖƵ°°×(inhibitors of apoptosis protein, IAP)±í´ï£¬ ¶øºóÕßÏÞÖÆÁ˾ÞÊÉϸ°ûµÄ¿ÉËÜÐԱ仯£¬ ²¢Ï÷Èõ·ÎÑ×ÒÂÔ­Ìå¸ÐȾËùÔì³ÉµÄÃâÒߴ̼¤[13]¡£

¡¡¡¡ÒÔÉÏÑо¿ÌáʾÒÂÔ­ÌåÄܹ»ÔÚM2Ð;ÞÊÉϸ°ûÖг¤ÆÚÉú´æ£¬ ËäÈ»M1Ð;ÞÊÉϸ°û×èÖ¹ÒÂÔ­ÌåµÄ¸´ÖÆÈ´ÎÞ·¨ÍêÈ«½«ÆäÇå³ý£¬ ΪÒÂÔ­ÌåÌÓ±ÜÃâÒßÓ¦´ðÒÔ¼°³ÖÐøÐÔ¸ÐȾ´´ÔìÁË»ú»á¡£ÒÂÔ­Ìå¿ÉÄÜͨ¹ýÏÞÖƾßÓп¹ÒÂÔ­Ìå×÷ÓõÄM1Ð;ÞÊÉϸ°û»î»¯£¬ ´Ù½øM0¡¢ M1Ð;ÞÊÉϸ°ûÏòM2Ð;ÞÊÉϸ°û¼«»¯£¬ Ϊ×ÔÉíÉú´æÓë·±Ö³´´Ôì¸üÓÐÀûµÄÌõ¼þ¡£

¡¡¡¡2¡¢ ÒÂÔ­ÌåÒÖÖÆËÞÖ÷ÃâÒßÓ¦´ð

¡¡¡¡¹ÌÓÐÃâÒßÊÇ»úÌåµÖ¿¹²¡Ô­ÌåÈëÇֵĵÚÒ»µÀ·ÀÏߣ¬ ÓɹÌÓÐÃâÒßÆÁÕÏ¡¢ ¹ÌÓÐÃâÒß·Ö×ÓºÍ×îΪ¹Ø¼üµÄ¹ÌÓÐÃâÒßϸ°û×é³É¡£¸ºÔðÃâÒß·ÀÓùµÄµ¥ºËÍÌÊÉϸ°ûϵͳ¡¢ ·¢»ÓÍÌÊɺÍɱÉËЧӦµÄÖÐÐÔÁ£Ï¸°û¡¢ ά³Ö×ÔÉíÃâÒßÄÍÊܵÄ×ÔȻɱÉË(natural killer, NK)ϸ°û¡¢ Á¬½Ó¹ÌÓÐÃâÒߺÍÊÊÓ¦ÐÔÃâÒßµÄÊ÷ͻ״ϸ°û(dendritic cells, DC)µÈ¹ÌÓÐÃâÒßϸ°û[14], ÒÔ¼°²ÎÓë»úÌåËùÓÐÃâÒßÓ¦´ðµÄTϸ°û£¬ ¾ùÔÚÃâÒßÓ¦´ðµÄÓÕµ¼Óëµ÷½ÚÖÐÆð×ÅÖØÒª×÷Óá£Òò´Ë£¬ Ñо¿ÒÂÔ­ÌåÓëÕâЩ¹ÌÓÐÃâÒßϸ°ûµÄÏ໥×÷Ó㬠ÒÔ¼°ÒÂÔ­Ìå¸ÐȾÈçºÎÌÓ±ÜÕâЩÃâÒßϸ°ûµÄ¹¥»÷£¬ ¶ÔÓÚ½âÎöÒÂÔ­Ìå¸ÐȾÖ²¡»úÖÆÖÁ¹ØÖØÒª¡£

¡¡¡¡2.1¡¢ ÒÂÔ­ÌåÉϵ÷IL-10ÏÞÖƾÞÊÉϸ°ûµÄÃâÒßÓ¦´ð

¡¡¡¡µ±²¡Ô­ÌåÈëÇÖ»úÌåʱ¿É´¥·¢Ñ×Ö¢·´Ó¦£¬ µ¼ÖÂÄÚ»·¾³Ê§ºâ£¬ Ëæºó»úÌåÆô¶¯¿¹Ñ×Ó¦´ð(anti-inflammatory response, AIR)ά³ÖÄÚ»·¾³ÎÈ̬¡£ÆäÖÐAIRÔںܴó³Ì¶ÈÉÏÊÜ°×ϸ°û½éËØ10( interleukin 10, IL-10)¿ØÖÆ£¬ IL-10ÊÇÒ»ÖÖÖ÷ÒªµÄÃâÒßÒÖÖÆÒò×Ó£¬ ¿ÉÏÞÖƹý¶ÈµÄTϸ°ûÓ¦´ð¡¢ Ñ×Ö¢½éÖʵÄÊͷźÍÖ÷Òª×éÖ¯ÏàÈÝÐÔ¸´ºÏÌå¢ò( major histocompatibility complex ¢ò, MHC¢ò) µÄ±í´ïµÈ¡£È»¶ø£¬ IL-10µÄȱ·¦Ôì³ÉÎÞÐÝÖ¹µÄÃâÒß¼¤»î£¬ Òý·¢Àà·çʪÐԹؽÚÑ×µÈÏà¹Ø¼²²¡£» ¶øIL-10µÄ¹ý¶È±í´ïµ¼Ö²»Á¼µÄÃâÒßÒÖÖÆ£¬ ¼ä½ÓµÄ´Ù½ø²¡Ô­Ìå´óÁ¿·±Ö³ÓëÀ©É¢[15]¡£

¡¡¡¡ÓÐÑо¿±íÃ÷ɳÑÛÒÂÔ­Ìå¸ÐȾ¾ÞÊÉϸ°ûºó´Ì¼¤IL-10²úÉú¡£ ËäÈ»¾ÞÊÉϸ°ûÊÇÔì³É²¡ÀíÐÔÑ×Ö¢µÄÖ÷Ҫϸ°û£¬ Ò²ÊÇÍÌÊÉɱ¾úµÄÖ÷Á¦£¬ µ«ÔÚIL-10Ô¤´¦ÀíºóÔÙ¸ÐȾµÄM1Ð;ÞÊÉϸ°ûÖй۲쵽°ûÄÚÒÂÔ­ÌåÔØÁ¿Ôö¼Ó¡¢ °üº­ÌåÌå»ýÔö´óµÄÏÖÏó¡£Ñо¿Õßͨ¹ýTranswellTMʵÑé½øÒ»²½Ö¤Êµ£º ɳÑÛÒÂÔ­Ìå¸ÐȾµÄM2Ð;ÞÊÉϸ°ûͨ¹ýÅÔ·ÖÃÚIL-10×÷ÓÃÓÚ¸ÐȾµÄM1Ð;ÞÊÉϸ°û£¬ ÒÖÖÆÆ俹ÒÂÔ­Ìå×÷Ó㬠²¢½â³ý¶ÔÒÂÔ­ÌåÉú³¤·±Ö³µÄÏÞÖÆ[16]¡£´ËÍ⣬ SanchezµÈ[17]֤ʵÊóÒÂÔ­Ìå¸ÐȾ¿ÉʹBϸ°ûÓÕµ¼´óÁ¿µÄIL-10²úÉú£¬ ÒÖÖÆTϸ°ûµÄÃâÒßÓ¦´ð£¬ µ¼ÖÂϸ¾úµÄÇå³ýÂʽµµÍ¡£¶Ô´Ë£¬ Del RíoµÈ[18]¹¹½¨ÁËIL-10¹ýÁ¿±í´ïµÄת»ùÒòСÊóÄ£ÐÍ£¬ ·¢ÏÖת»ùÒòСÊó¸ÐȾºóÖ¢×´±ÈÒ°ÉúÐÍСÊó¸üΪÑÏÖØ£¬ ÇÒ×éÖ¯ÖÐÒÂÔ­ÌåÔØÁ¿¸ü¸ß£¬ Ñ×ÐÔ²¡ÔîÖÜΧÃâÒßÑôÐÔϸ°ûÒ²Ïà¶ÔÔö¶à£¬ ×ÔÉí¿¹ÒÂÔ­ÌåÃâÒߺÄʱ¸ü³¤£» ²¢ÇÒ£¬ ¸Ãת»ùÒòСÊóÌåÄÚ¾ÞÊÉϸ°ûļ¼¯ÊÜË𣬠ÒÂÔ­Ìå¸ÐȾʱ»î»¯µÄ¾ÞÊÉϸ°ûÊýÁ¿Ã÷ÏÔϽµ¡£Ïà·´£¬ IL-10»ùÒòÇóýСÊóÌåÄÚÒÂÔ­ÌåÇå³ýËÙÂÊÔö¼Ó£¬ 1Ð͸¨ÖúT(T helper type 1, Th1)ϸ°ûÃâÒßÔöÇ¿£¬ ÇÒδ¼ûÉÏÉúÖ³µÀËðÉË[19]¡£

¡¡¡¡ÒÂÔ­Ìåͨ¹ýIL-10µÄÃâÒßÒÖÖÆ×÷ÓÃÈëÇÖ»úÌåºó£¬ ´Ì¼¤Bϸ°û¡¢ ¾ÞÊÉϸ°û¡¢ DCµÈÊÍ·ÅIL-10, ½øÒ»²½·Å´ó¸ÃЧӦ¡£IL-10/Janus¼¤Ã¸1(Janus kinase 1, JAK1)ÐźÅתµ¼×ÓÓëת¼¼¤»î×Ó3(signal transducers and activators of transcription 3, STAT3)¼¶Áª·´Ó¦±»¼¤»î£¬ Á×ËữµÄSTAT3Ò×λ½øÈëϸ°ûºËÓëºËÄÚSmad½áºÏÔª¼þ(Smad-binding element, SBE)ÇøÓòIL-10°Ð»ùÒòµÄÆô¶¯×Ó½áºÏ£¬ µ¼ÖÂÃâÒßµ÷½Ú±í´ïÆ׸ıä[20], ×îÖÕʵÏÖ×ÔÉíµÄ³ÖÐøÐÔ¸ÐȾ¡£´ËÍ⣬ ÔÚÒÂÔ­ÌåÒÖÖÆËÞÖ÷µòÍö[21]ÒÔ¼°¹¹½¨³ÖÐøÐÔ¸ÐȾģÐÍ[22]µÄÑо¿ÖоùÓÐSTAT3µÄ²ÎÓ룬 ÒÂÔ­ÌåÊÇ·ñ×÷ÓÃÓÚSTAT3À´ÊµÏÖ¶ÔËÞÖ÷ÃâÒßÓ¦´ðµÄµ÷½ÚÓдý½øÒ»²½Ñо¿¡£

¡¡¡¡2.2 ¡¢ÒÂÔ­Ìå¸ÐȾʹÖÐÐÔÁ£Ï¸°û°ûÍâÓÕ²¶Íø(neutrophil extracellular traps, NET)Âé±Ô

¡¡¡¡ÖÐÐÔÁ£Ï¸°ûÊÇ»úÌåÖÐ×î·á¸»µÄ¹ÌÓÐÃâÒßϸ°û£¬ Ò²ÊÇËÞÖ÷·ÀÓù»úÖƵĹؼü¡£µ±²¡Ô­ÌåÈëÇÖʱ£¬ ÖÐÐÔÁ£Ï¸°ûͨ¹ý²úÉúROS[23]¡¢ ÍÌÊÉ×÷ÓᢠÍÑ¿ÅÁ£ÒÔ¼°·ÖÃÚϸ°ûÒò×ÓµÈÇå³ý²¡Ô­Ìå¡£³ý´ËÖ®Í⣬ ÖÐÐÔÁ£Ï¸°û»¹¿ÉÒÔͨ¹ýÊÍ·ÅNET²¶»ñºÍÏÞÖƲ¡Ô­Ìå[24]¡£NETµÄÐγÉÊÇÒ»ÖÖ½ø»¯Éϱ£ÊصÄÏÈÌìÃâÒßÓ¦´ð£¬ ÓÉÖÐÐÔÁ£Ï¸°û·ÖÃÚ¿ÅÁ£×´¿¹¾úµ°°×°ü¹üÈ¥Äý¼¯µÄºËDNA, ÐγÉDNA-µ°°×ÖÊɱ¾ú¾Û¼¯Ìå[25]¡£Òò´Ë£¬ ÔÚÒÂÔ­ÌåÌÓ±ÜËÞÖ÷ÃâÒߵĻúÖÆÑо¿ÖУ¬ ̽ÌÖÒÂÔ­ÌåÈçºÎ¶ã±ÜÖÐÐÔÁ£Ï¸°ûµÄÍÌÊÉ×÷ÓÃÒÔ¼°NETµÄ²¶»ñ×îΪ¹Ø¼ü¡£

¡¡¡¡×î½üµÄÑо¿½«É³ÑÛÒÂÔ­Ìå¶ÔÖÐÐÔÁ£Ï¸°ûɱ¾úÐźŵĸÉÈŹéÒòÓÚÒÂÔ­Ìåµ°°×øÑù»îÐÔÒò×Ó(Chlamydial-protease-like activity factor, CPAF)[26]¡£CPAFÊÇÒ»ÖÖ±£ÊصÄË¿°±Ëáµ°°×ø£¬ ½èÖú¢òÐÍ·ÖÃÚϵͳ·ÖÃÚµ½ËÞÖ÷ϸ°ûÖÊÖУ¬ ¾ßÓнÏÇ¿µÄµ°°×Ë®½â»îÐԺ͵×ÎïÌØÒìÐÔ£¬ ¿ÉÒÖÖÆCXCÇ÷»¯Òò×ÓÅäÌå10(C-X-C motif chemokine ligand 10, CXCL10)µÈϸ°ûÇ÷»¯Òò×Ó·ÖÃÚ£¬ ÆÆ»µËÞÖ÷ÃâÒßÓ¦´ð£¬ ÔÚÃâÒßÌÓ±ÜÖÐÆð×ÅÖØÒª×÷ÓÃ[27]¡£ËæÒÂÔ­Ìå´ÓÆÆÁѵÄËÞÖ÷ϸ°ûÖÐÊÍ·Åºó£¬ CPAFÇиîÖÐÐÔÁ£Ï¸°û±íÃæ¼×õ£ëÄÊÜÌå2(formyl peptide receptor 2, FPR2), ×è¶ÏÆäÏÂÓÎÐźÅתµ¼£¬ ÆäÖаüÀ¨¶ÔNET²úÉúÆð¹Ø¼ü×÷ÓõÄÁ×Ö¬õ£¼¡´¼3-¼¤Ã¸(phosphatidylinositol 3-kinase, PI3K)ÐźÅͨ·£¬ ×îÖÕµ¼ÖÂÖÐÁ£Ï¸°û±»Âé±Ô£¬ ÎÞ·¨²úÉúNET, ¶øÒÂÔ­Ìå¼ÌÐøÔÚËÞÖ÷ϸ°ûÄÚ´æ»î²¢¿ªÊ¼¸´ÖÆ[28]¡£YangµÈ[29]»¹·¢ÏÖȱ·¦CPAFµÄL2-17ɳÑÛÒÂÔ­Ìå¾úÖêÔÚСÊóÏÂÉúÖ³µÀ½ÓÖÖ¼¸Ììºó¾Í±»Çå³ý£¬ ÎÞ·¨Íê³É¶¨Ö³£¬ ¶ø±í´ïCPAFµÄL2-5ɳÑÛÒÂÔ­Ìå¾úÖê¿ÉÔÚСÊóÏÂÉúÖ³µÀ¶¨Ö³³¤´ï3ÖÜ¡£ÆäÖÐL2-17ɳÑÛÒÂÔ­ÌåºÍL2-5ɳÑÛÒÂÔ­Ì嶼±£³ÖºÜÇ¿µÄ¸ÐȾÁ¦£¬ ¾ùÄܳɹ¦¸ÐȾÉÏÉúÖ³µÀ£¬ Õâ¼ä½Ó˵Ã÷CPAF¿ÉÒÔ´Ù½øɳÑÛÒÂÔ­ÌåÔÚËÞÖ÷ϸ°ûÖеĴæ»î¡£

¡¡¡¡Êµ¼ÊÉÏ£¬ ÖÐÐÔÁ£Ï¸°û»¹²ÎÓëÆäËûÖÚ¶àµÄ¿¹ÒÂÔ­ÌåÃâÒßÓ¦´ð¡£QiaoµÈ[30]·¢ÏÖ·ÎÑ×ÒÂÔ­Ìå¸ÐȾ¿ÉÉϵ÷ÖÐÐÔÁ£Ï¸°ûÏà¹ØÇ÷»¯Òò×Ó[Èç¾ÞÊÉϸ°ûÑ×ÐÔµ°°×2(macrophage inflammatory protein 2, MIP-2)ºÍIL-6]ÒÔ¼°Ï¸°û¼ä𤸽·Ö×Ó1(intercellular cell adhesion molecule-1, ICAM-1)ºÍѪ¹Üϸ°û𤸽·Ö×Ó1(vascular cell adhesion molecule-1, VCAM-1)µÈ𤸽·Ö×ӵıí´ï£¬ ʹÖÐÐÔÁ£Ï¸°ûÏò¸ÐȾ²¿Î»Éø͸¡£¶øÔÚIL-17ȱ·¦»ò×è¶ÏÄÚÔ´ÐÔIL-17AµÄСÊóÄ£ÐÍÌåÄÚ·¢ÏÖÉϵ÷µÄMIP-2ºÍIL-6¼õÉÙ£¬ ´Ó¶øµ¼Ö·ÎÖÐÐÔÁ£Ï¸°ûļ¼¯¼õÉÙ¡£LehrµÈ[31]֤ʵЯ´øÒþ±ÎÖÊÁ£µÄɳÑÛÒÂÔ­Ìå¿É´¥·¢¸ÐȾÉúÖ³µÀÉÏƤϸ°û¿ÉÈÜÐÔÒò×ӵĿìËÙÊÍ·Å£¬ µ¼ÖÂÖÐÐÔÁ£Ï¸°ûÏò¸ÐȾ²¿Î»Ä¼¼¯£¬ ͬʱ´Ë²¿Î»µÄÖÐÐÔÁ£Ï¸°ûÊÙÃüÑÓ³¤£¬ Ôì³ÉÑ×Ö¢²¿Î»µÄ×éÖ¯ËðÉË¡£ÉÆÓÚ²ØÄäµÄÒÂÔ­ÌåÊÇ·ñÄܹ»½èÖúIL-17µÄȱ·¦¡¢ Òþ±ÎÖÊÁ£±àÂëµÄ¶¾Á¦Òò×Ó[32]µÈÆäËûµÄ·½Ê½¸ÉÈÅËÞÖ÷ÃâÒßÓ¦´ð£¬ ´Ó¶ø½ø»¯³öеÄÃâÒßÌÓÒÝ»úÖÆÈÔÓдý½øÒ»²½Ñо¿¡£

¡¡¡¡2.3¡¢ ÒÂÔ­Ìå¸ÐȾʹTϸ°ûºÄ½ß

¡¡¡¡ÔÚ¶àÖÖÂýÐÔ¸ÐȾ¼°°©Ö¢µÄÑо¿ÖÐ֤ʵ£¬ ³ÌÐòÐÔϸ°ûËÀÍöµ°°× 1(programmed death 1, PD-1)µÄÔö¼Ó±íÃ÷Tϸ°ûºÄ½ß¡£PD-1ÓëÆäÔÚ¿¹Ô­Ìá³Êϸ°ûÉϵijÌÐòÐÔϸ°ûËÀÍöµ°°×1ÅäÌå1 ( programmed death 1 ligand 1, PD-L1)½áºÏ£¬ ÒÖÖÆTϸ°ûÊÜÌåÐźŴ«µ¼½éµ¼µÄ»î»¯£¬ ´Ó¶øʹTϸ°û½øÈ듾«Æ£Á¦½ß”µÄ״̬£¬ ±íÏÖΪʧȥЧӦTϸ°û¹¦ÄÜ¡¢ ¸ßˮƽÒÖÖÆÊÜÌå³ÖÐø±í´ï¡¢ ÃâÒß¼ÇÒäȱÏÝ¡¢ ´úлʧµ÷µÈ¡£¶ø×è¶ÏPD-1ÓëPD-L1µÄÏ໥×÷ÓÿÉÒÔÄæתÕâÖֺĽßÐÔTϸ°û(exhausted T cells, Tex), »Ö¸´Tϸ°ûµÄ»îÐÔÓ빦ÄÜ[33], Òò´Ë£¬ PD-1/PD-L1ÊÓΪTϸ°ûºÄ½ßµÄ±êÖ¾Î ¶ø¸ÉÈÅPD-1»òÆäÅäÌåµÄ¿¹ÌåºÍϸ°ûÃâÒßÁÆ·¨Òѱ»Ö¤Êµ¾ßÓÐÁÙ´²ÒâÒå¡£

¡¡¡¡ÔÚÒÂÔ­ÌåµÄ¸ÐȾÖÐÒ²´æÔÚCD8+Tϸ°ûµÄºÄ½ß¡£FankhauserµÈ[34]ÔÚɳÑÛÒÂÔ­Ìå¼±ÐÔ¸ÐȾÆÚ¶Ô×Ó¹¬ÄÚ²»Í¬ÃâÒßÒÖÖÆÊÜÌå(inhibitory receptors, IR)ºÍÅäÌå½øÐÐÁ˼ì²â£¬ ·´×ªÂ¼PCR½á¹ûÏÔʾPD-L1¸ß±í´ï¡£¶ø×è¶ÏPD-L1¿Éʹԭ·¢ÐÔ¸ÐȾÆÚ¼äÒÂÔ­ÌåµÄÇå³ýÂÊÔö¼Ó£¬ µ«¶Ô¼Ì·¢ÐÔ¸ÐȾÎÞÓ᣿¹CD8+Tϸ°ûºÄ½ß¿¹ÌåµÄ¸øÒ©ÌáʾÇå³ýÒÂÔ­ÌåµÄÄÜÁ¦Ã»ÓвîÒ죬 Õâ±íÃ÷¼ÇÒäCD8+ Tϸ°ûµÄÀ©ÔöÄÜÁ¦Êܵ½Ë𺦡£¼Ì·¢¸ÐȾÆÚ¼äµÄÕâÖÖ¼ÇÒäÃâÒßȱÏݹéÒòÓÚ±»¸ÐȾСÊó×Ó¹¬ÖÐPD-L1µÄ¸ßˮƽ±í´ï£¬ µ¼ÖÂËÞÖ÷¶Ôϸ¾úµÄÇå³ýÄÜÁ¦ÊÜËð¡£´ËÍ⣬ ÓÐÑо¿·¢ÏÖÔÚDCÉϱí´ïµÄPD-L1±£»¤ÆäÃâÊÜNKϸ°ûµÄɱÉË£¬ µ«Í¬Ê±Ò²ÒÖÖÆÁË×ÔÉíµÄÃâÒßÓ¦´ð[35]¡£ÒÂÔ­ÌåÕýÊÇÀûÓÃÁËPD-1¶ÔTϸ°û¡¢ Bϸ°ûµÄÔöÖ³ºÍϸ°ûÒò×Ó·ÖÃÚµÄÒÖÖÆ£¬ ÒÔÌÓ±ÜËÞÖ÷µÄÃâÒßÓ¦´ð¡£

¡¡¡¡½üÄêÀ´£¬ ÁíÒ»¸öTϸ°û±íÃæÒÖÖÆ·Ö×ÓTϸ°ûÃâÒßÇòµ°°×Óë𤵰°×½á¹¹Óò3(T cell immunoglobulin and mucin domain-3, TIM-3)³ÉΪÃâÒßÁÆ·¨µÄабꡣTIM-3ÊÇÒ»ÖֻÒÖÖÆ·Ö×Ó£¬ ÔÚTϸ°û¡¢ NKϸ°û¡¢ DC¡¢ µ¥ºËϸ°ûµÈϸ°û±íÃæ¾ù¿É±í´ï£¬ ²ÎÓëµ÷¿Ø¹¦ÄÜʧµ÷»òºÄ½ßµÄTϸ°û¡£ÆäÓëÅäÌå°ëÈéÌÇÄý¼¯ËØ9(galectin-9)½áºÏ£¬ ÓÕµ¼°ûÄÚÈËÀà°×ϸ°û¿¹Ô­BÏà¹Øת¼±¾3((HLA-B-associated transcript 3, BAT3)ÊÍ·Å£¬ µ¼ÖÂTϸ°û¹¦ÄÜÒÖÖÆ»òËÀÍö£» Óë°©Åß¿¹Ô­Ïà¹Øϸ°û𤸽·Ö×Ó1(carcinoembryonic antigen related cellular adhesion molecule 1, CEACAM1)ÐγÉTIM3-CEACAM1Öᣬ ¶ÔTϸ°ûºÍËèϵϸ°ûµÄ˳ʽ»ò·´Ê½ÃâÒßÓ¦´ðÆðÒÖÖÆ×÷Óá£ÔÚÖ×ÁöÖÎÁƹý³ÌÖУ¬ ÁªºÏ×è¶ÏTIM-3ÓëPD-1¿ÉÔöÇ¿¿¹Ö×ÁöµÄÃâÒßÓ¦´ð[36]¡£¶øÔÚÈËÀàÃâÒßȱÏݲ¡¶¾(human immunodeficiency virus, HIV)¸ÐȾ¹ý³ÌÖУ¬ TIM-3ÔÚCD4+ Tϸ°ûºÍCD8+ Tϸ°ûÉϾùÓÐÉϵ÷£¬ Æä±í´ïÓëHIVÔØÁ¿³ÊÕýÏà¹Ø£¬ ÓëTϸ°û¾ø¶ÔÊý³Ê¸ºÏà¹Ø£» ÔÚ±ûÐ͸ÎÑײ¡¶¾¸ÐȾÖУ¬ TIM-3 ÊÇTexϸ°ûµÄ±êÖ¾£» ÔÚ½áºÏ·ÖÖ¦¸Ë¾ú¸ÐȾÆÚ¼äҲ֤ʵTIM-3+ Tex´æÔÚ[37]¡£¶øÒÂÔ­ÌåÄÜ·ñÒ²ÀûÓÃPD-1¡¢ TIM-3µÈÒÖÖÆ·Ö×ÓÀ´×è°­Tϸ°ûÓ¦´ð£¬ ʵÏÖÃâÒßÌÓÒÝ£¬ ÈÔÓдýÑо¿¡£

¡¡¡¡3 ¡¢ÒÂÔ­ÌåÒÖÖÆËÞÖ÷ϸ°ûµòÍö

¡¡¡¡ÒÂÔ­ÌåµÄ¸´ÖÆÒÀÀµÓÚËÞÖ÷ϸ°ûATPºÍһЩ¸ßÄÜ´úл²úÎ ±ÜÃâËÞÖ÷ϸ°ûËÀÍöÊÇÒÂÔ­Ìå°ûÄÚÉú´æºÍÔöÖ³µÄ¹Ø¼ü£¬ Ϊ´ËÒÂÔ­Ìå²»¶ÏÑ°Çó¸÷ÖÖ²ßÂÔά³ÖËÞÖ÷ϸ°û»îÐÔ£¬ ÒÔÍê³ÉÆä·¢ÓýÖÜÆÚ(ͼ2)¡£

¡¡¡¡ÒÂÔ­Ìåͨ¹ý¸ÉÈÅËÞÖ÷ϸ°ûÐźÅתµ¼»ñÈ¡ÓªÑøÖ§³Ö£¬ ×è¶ÏËÞÖ÷ϸ°ûÄÚÔ´ÐÔ»òÍâÔ´ÐÔµòÍö£¬ ÔÚÆ临Öƽ׶κ͸ÐȾºóÆÚÔì³ÉµÄËÞÖ÷ϸ°û´úл¸ºµ££¬ µ¼ÖÂһЩӦ¼¤Ïà¹Øͨ·Æô¶¯¡£Êó˫΢Ìå»ùÒò2(murine double minute 2, MDM2)Êǵ°°×¼¤Ã¸B(protein kinase B, PKB/AKT)ͨ·ÏÂÓεÄÒ»¸ö×÷Óõ×Î ÒÂÔ­Ìå¸ÐȾ¿ÉʹÆäºË¶¨Î»ÐòÁи½½üµÄµÚ166ºÍ186λ˿°±ËáÁ×Ëữ£¬ ´Ó¶øµ¼Ö°ûÖÊÖÐAKT-MDM2¸´ºÏÎïѸËÙ½âÀë¡¢ MDM2½øÈëϸ°ûºË²¢Óëp53½áºÏ£¬ MDM2-p53Ï໥×÷ÓÃÖἤ»îºó½µ½âp53, ´ÙʹÒÂÔ­Ìå²ÎÓëµ÷½ÚÓ¦¼¤·´Ó¦£¬ ʵÏÖ¿¹µòÍö×÷ÓÃ[38]¡£ÒÂÔ­Ìå¸ÐȾºóÆÚ£¬ Æä·¢Óý±ØÐèµÄ3-Á×Ëἡ´¼ÒÀÀµµÄµ°°×¼¤Ã¸1(3-phosphoinositide-dependent protein kinase 1, PDPK1)±»Ä¼¼¯µ½°üº­ÌåÖУ¬ Myc»ùÒò±í´ïÔö¼Ó£¬ ʹ¼ºÌǼ¤Ã¸¢ò(hexokinase ¢ò, HK2)ÏòÏßÁ£Ì帻¼¯¡£Ëæºó£¬ HK2ÓëµçѹÒÀÀµÐÔÒõÀë×ÓͨµÀ1(voltage dependent anion channel 1, VDAC1)µÄ½áºÏµ¼ÖÂÌǽͽâºÍÑõ»¯´úлËÙÂÊÔö¼Ó£¬ ¾ºÕùÒÖÖƵòÍöÐźÅ[39]¡£´ËÍ⣬ ·ÎÑ×ÒÂÔ­Ìå¸ÐȾÖÐÐÔÁ£Ï¸°ûʹPI3K/AKTºÍϸ°ûÍâÐźŵ÷½Ú¼¤Ã¸1/2(extracellular signal-regulated kinases 1/2, ERK1/2)ͨ·»î»¯£¬ ά³Ö¿¹µòÍöµ°°×¹ÇËèϸ°û°×Ѫ²¡µ°°×1(myeloid cell leukemia 1, Mcl-1)µÄ±í´ï£» Ëæºó£¬ ºËÒò×ÓκB(nuclear factor kappa-B, NF-κB)ÒÀÀµÐÔIL-8µÄÊÍ·ÅҲʹMcl-1³ÖÐø±í´ï£¬ ¹²Í¬ÑÓ³ÙÖÐÐÔÁ£Ï¸°ûµÄµòÍö[27]¡£´ËÍ⣬ ɳÑÛÒÂÔ­Ìå¸ÐȾÉÏƤϸ°û¿É×èÖ¹Ö×Áö»µËÀÒò×Ó(tumor necrosis factor, TNF)/Ö×Áö»µËÀÒò×ÓÊÜÌå(tumor necrosis factor receptor, TNFR)¸´ºÏÎïÄÚ»¯£¬ ÇжÏë×Ììµ°°×ø8(caspase-8)»î»¯µÄÉÏÓÎÐźţ¬ µ¼ÖÂËÞÖ÷ϸ°ûcaspase-8-caspase-3»î»¯Í¾¾¶ºÍÏßÁ£ÌåµòÍö;¾¶Ë«ÖØÊÜ×è¡£ÉõÖÁÔÚµòÍöµ°°×ÒÖÖÆÎï(inhibitor of apoptosis protein, IAP)»òϸ°ûcaspase-8 FADDÑù°×ϸ°û½éËØβת»¯Ã¸(FADD-like interleukin beta-coverting enzyme, FLICE)]ÑùÒÖÖƵ°°×(cellular FlLICE-like inhibitory protein, cFLIP)ȱʧµÄÇé¿öÏ£¬ ÒÂÔ­ÌåÈÔÄÜ×èÖ¹¸ÐȾϸ°ûµÄµòÍö£¬ ²¢Î¬³Ö·ÇµòÍöTNFÐźŵÄÕý³£×ªµ¼[40]¡£

¡¡¡¡´ËÍ⣬ SixtµÈ[41]·¢ÏÖÒÂÔ­Ìå°üº­ÌåĤµ°°×ÖÐÒÂÔ­ÌåÉú´æÆô¶¯×Ó(Chlamydia promoter of survival, CpoS)¿ÉÒÔÌṩ¾Ö²¿µÄ¿¹µòÍö±£»¤×÷Óá£ÒÂÔ­Ìå¸ÐȾ¿ÉÒÔÒýÆðËÞÖ÷ϸ°ûTNF-α¡¢ IFN-γµÈϸ°ûÒò×Ó²úÉú£¬ CpoSʧ»îÄÜÔöÇ¿ËÞÖ÷ϸ°û²úÉúϸ°ûÒò×ӺʹÙËÀÍöÐźŵÄÄÜÁ¦£¬ ¿ÉÓÕµ¼¸ÐȾϸ°ûѸËÙµòÍöºÍ»µËÀ¡£ÔöÇ¿µÄϸ°ûÒò×ÓÓ¦´ðÌáʾËÞÖ÷ϸ°û¶ÔCpoSȱÏݵİüº­ÌåÃô¸Ð£¬ ±íÃ÷CpoS¿ÉÒÔÑÚ¸ÇËÞÖ÷ϸ°ûµÄÒÂÔ­ÌåÐźÅÀ´µÖÏûϸ°û×ÔÖ÷·ÀÓù³ÌÐò£¬ ʵÏÖ±£»¤×÷Óá£

¡¡¡¡Í¼2 ÒÂÔ­ÌåÃâÒßÌÓÒÝ»úÖÆ
ͼ2 ÒÂÔ­ÌåÃâÒßÌÓÒÝ»úÖÆ

¡¡¡¡4 ¡¢Ð¡½áºÍÕ¹Íû

¡¡¡¡³ýÁËÏÈÇ°ÒÑÖªµÄÒÂÔ­ÌåÌÓ±ÜËÞÖ÷ϸ°ûµÄÍÌÊÉÈںϡ¢ ϵ÷MHCµÄ±í´ï¡¢ ¸ÉÈÅÐźÅתµ¼µÈÃâÒßÌÓÒÝ»úÖÆ£¬ ÒÂÔ­ÌåÒѽø»¯³ö¶àÖÖÃâÒßÌÓÒÝÊֶΣ¬ ʵÏÖÔÚËÞÖ÷ϸ°ûÄڵij¤ÆÚ´æ»îÓë·±Ö³¡£ÒÂÔ­ÌåÊÇ·ñÄÜͨ¹ýÂé±ÔNET¡¢ ´Ù½øM1ÏòM2Ð;ÞÊÉϸ°ûת±ä¡¢ ºÄ½ßTϸ°ûµÈÊÖ¶Î×è°­ÃâÒßϸ°ûÕý³£¹¦ÄÜÀ´±£»¤×ÔÉí?TIM3¡¢ STAT3¡¢ IL-17µÈ×÷Ó÷Ö×ÓÊÇ·ñÊÇÒÂÔ­ÌåʵÏÖÃâÒßÌÓÒݵÄÍ»ÆƵã?¼ÌÐøÑо¿ÒÂÔ­ÌåÓëËÞÖ÷ÃâÒßϸ°ûµÄÏ໥×÷Ó㬠ÒÔ¼°ÒÂÔ­Ìå¸ÐȾËùÖÂËÞÖ÷ÖÚ¶àÃâÒßϸ°ûÖ®¼äµÄÏ໥×÷ÓÃÊÇ̽Ã÷ÒÂÔ­Ìå³ÖÐøÐÔ¸ÐȾµÄÃâÒßÌÓÒÝ»úÖƵÄÖص㣬 Ò²ÊÇÑз¢ÒÂÔ­Ìå¸ÐȾËùÖ¼²²¡ÒßÃçµÄÖØÒª»ù´¡¡£

¡¡¡¡²Î¿¼ÎÄÏ×

¡¡¡¡[1] Banhart S,Sch?fer E K,Gensch J M,et al.Sphingolipid metabolism and transport in Chlamydia trachomatis and Chlamydia psittaci infections[J/OL].Front Cell Dev Biol,2019,7:223.DOI:10.3389/fcell.2019.00223.eCollection 2019.
¡¡¡¡[2] Mattmann P,Marti H,Borel N,et al.Chlamydiaceae in wild,feral and domestic pigeons in Switzerland and insight into population dynamics by Chlamydia psittaci multilocus sequence typing[J/OL].PLoS One,2019,14(12):e0226088.DOI:10.1371/journal.pone.0226088.eCollection 2019.PMID:31887111.
¡¡¡¡[3] Lausen M,Pedersen M S,Rahman N S K,et al.Opsonophagocytosis of Chlamydia pneumoniae by human monocytes and neutrophils[J/OL].Infect Immun,2020,88(7):e00087-20.DOI:10.1128/IAI.00087-20.Print 2020 Jun 22.
¡¡¡¡[4] Keb G,Fields K A.An ancient molecular arms race:Chlamydia vs.membrane attack complex/perforin (MACPF) domain proteins[J/OL].Front Immunol,2020,11:1490.DOI:10.3389/fimmu.2020.01490.
¡¡¡¡[5] Weiss E.The effect of antibiotics on agents of the psittacosis-lymphogranuloma group.¢ñ.The effect of penicillin[J].J Infect Dis,1950,87(3):249-263.
¡¡¡¡[6] Panzetta M E,Valpia R H,Saka H A.Chlamydia persistence:A survival strategy to evade antimicrobial effects in-vitro and in-vivo[J/OL].Front Microbiol,2018,9:3101.DOI:10.3389/fmicb.2018.03101.eCollection 2018.
¡¡¡¡[7] Slade J A,Brockett M,Singh R,et al.Fosmidomycin,an inhibitor of isoprenoid synthesis,induces persistence in Chlamydia by inhibiting peptidoglycan assembly[J/OL].PLoS Pathog,2019,15(10):e1008078.DOI:10.1371/journal.ppat.1008078.eCollection 2019.
¡¡¡¡[8] Marangoni A,Zalambani C,Marziali G,et al.Low-dose doxycycline induces Chlamydia trachomatis persistence in HeLa cells[J/OL].Microb Pathog,2020,147:104347.DOI:10.1016/j.micpath.2020.104347.Epub 2020 Jun 17.
¡¡¡¡[9] Hatch N D,Ouellette S P.Inhibition of tRNA synthetases induces persistence in Chlamydia[J/OL].Infect Immun,2020,88(4):e00943-19.DOI:10.1128/IAI.00943-19.Print 2020 Mar 23.
¡¡¡¡[10] Foschi C,Bortolotti M,Polito L,et al.Insights into penicillin-induced Chlamydia trachomatis persistence[J/OL].Microb Pathog,2020,142:104035.DOI:10.1016/j.micpath.2020.104035.Online ahead of print.
¡¡¡¡[11] Gracey E,Lin A,Akram A,et al.Intracellular survival and persistence of Chlamydia muridarum is determined by macrophage polarization[J/OL].PLoS One,2013,8(8):e69421.DOI:10.1371/journal.pone.0069421.eCollection 2013.
¡¡¡¡[12] Buchacher T,Ohradanova-Repic A,Stockinger H,et al.M2 polarization of human macrophages favors survival of the intracellular pathogen Chlamydia pneumoniae[J/OL].PLoS One,2015,10(11):e0143593.DOI:10.1371/journal.pone.0143593.eCollection 2015.
¡¡¡¡[13] Nadella V,Mohanty A,Sharma L,et al.Inhibitors of apoptosis protein antagonists (Smac mimetic compounds) control polarization of macrophages during microbial challenge and sterile inflammatory responses[J/OL].Front Immunol,2017,8:1792.DOI:10.3389/fimmu.2017.01792.eCollection 2017.
¡¡¡¡[14] Wang H,Li J,Dong X,et al.NK cells contribute to protective memory T cell mediated immunity to chlamydia muridarum infection[J/OL].Front Cell Infect Microbiol,2020,10:296.DOI:10.3389/fcimb.2020.00296.
¡¡¡¡[15] Saraiva M,Vieira P,O'Garra A.Biology and therapeutic potential of interleukin-10[J/OL].J Exp Med,2020,217(1):e20190418.DOI:10.1084/jem.20190418.
¡¡¡¡[16] Tietzel I,Quayle A J,Carabeo R A.Alternatively activated macrophages are host cells for Chlamydia trachomatis and reverse anti-chlamydial classically activated macrophages[J/OL].FrontMicrobiol,2019,10:919.DOI:10.3389/fmicb.2019.00919.eCollection 2019.
¡¡¡¡[17] Sanchez L R,Godoy G J,Gorosito Serrán M,et al.IL-10 producing B cells dampen protective T cell response and allow Chlamydia muridarum infection of the male genital tract[J/OL].Front Immunol,2019,10:356.DOI:10.3389/fimmu.2019.00356.eCollection 2019.
¡¡¡¡[18] Del Río L,Murcia A,Buendía A J,et al.Development of an in vivo model of Chlamydia abortus chronic infection in mice overexpressing IL-10[J].Vet Microbiol,2018,213:28-34.
¡¡¡¡[19] Vicetti Miguel R D,Quispe Calla N E,Dixon D,et al.IL-4-secreting eosinophils promote endometrial stromal cell proliferation and prevent Chlamydia-induced upper genital tract damage[J/OL] .Proc Natl Acad Sci U S A,2017,114(33):E6892-E6901.DOI:10.1073/pnas.1621253114.Epub 2017 Aug 1.
¡¡¡¡[20] Du K,Zhou M,Li Q,et al.Chlamydia trachomatis inhibits the production of pro-inflammatory cytokines in human PBMCs through induction of IL-10[J].J Med Microbiol,2018,67(2):240-248.
¡¡¡¡[21] Sun Y,Zhou P,Chen S,et al.The JAK/STAT3 signaling pathway mediates inhibition of host cell apoptosis by Chlamydia psittaci infection[J/OL].Pathog Dis,2017,75(7):ftx088.DOI:10.1093/femspd/ftx088.
¡¡¡¡[22] Yu P,Xiao L,Lin L,et al.STAT3-mediated TLR2/4 pathway upregulation in an IFN-gamma-induced Chlamydia trachomatis persistent infection model[J/OL].Pathog Dis,2016,74(6):ftw076.DOI:10.1093/femspd/ftw076.Epub 2016 Aug 7.
¡¡¡¡[23] Dong Y,Jin C,Ding Z,et al.TLR4 regulates ROS and autophagy to control neutrophil extracellular traps formation against Streptococcus pneumoniae in acute otitis media[J].Pediatr Res,2020 May 21.DOI:10.1038/s41390-020-0964-9.Online ahead of print.32438368.
¡¡¡¡[24] Mohanty T,Fisher J,Bakochi A,et al.Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis[J/OL].Nat Commun,2019,10(1):1667.DOI:10.1038/s41467-019-09040-0.
¡¡¡¡[25] Magán-Fernández A,Rasheed Al-Bakri S M,O'Valle F,et al.Neutrophil extracellular traps in periodontitis[J/OL].Cells,2020,9(6):1494.DOI:10.3390/cells9061494.
¡¡¡¡[26] Wong W F,Chambers J P,Gupta R,et al.Chlamydia and its many ways of escaping the host immune system[J/OL].J Pathog,2019,2019:8604958.DOI:10.1155/2019/8604958.eCollection 2019.
¡¡¡¡[27] Schott B H,Antonia A L,Wang L,et al.Modeling of variables in cellular infection reveals CXCL10 levels are regulated by human genetic variation and the Chlamydia-encoded CPAF protease[J/OL].Sci Rep,2020,10(1):18269.DOI:10.1038/s41598-020-75129-y.
¡¡¡¡[28] Rajeeve K,Das S,Prusty B K,et al.Chlamydia trachomatis paralyses neutrophils to evade the host innate immune response[J].Nat Microbiol,2018,3(7):824-835.
¡¡¡¡[29] Yang Z,Tang L,Shao L,et al.The Chlamydia-secreted protease CPAF promotes Chlamydial survival in the mouse lower genital tract[J].Infect Immun,2016,84(9):2697-2702.
¡¡¡¡[30] Qiao S,Zhang H,Zha X,et al.Endogenous IL-17A mediated neutrophil infiltration by promoting chemokines expression during chlamydial lung infection[J].Microb Pathog,2019,129:106-111.
¡¡¡¡[31] Lehr S,Vier J,H?cker G,et al.Activation of neutrophils by Chlamydia trachomatis-infected epithelial cells is modulated by the chlamydial plasmid[J].Microbes Infect,2018,20(5):284-292.
¡¡¡¡[32] Zhong G.Chlamydial plasmid-dependent pathogenicity[J/OL].Trends Microbiol,2017,25(2):141-152.
¡¡¡¡[33] Utzschneider D T,Gabriel S S,Chisanga D,et al.Early precursor T cells establish and propagate T cell exhaustion in chronic infection[J].Nat Immunol,2020,21(10):1256-1266.
¡¡¡¡[34] Fankhauser S C,Starnbach M N.PD-L1 limits the mucosal CD8+ T cell response to Chlamydia trachomatis[J].J Immunol,2014,192(3):1079-1090.
¡¡¡¡[35] Peng Q,Qiu X,Zhang Z,et al.PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade[J/OL].Nat Commun,2020,11(1):4835.DOI:10.1038/s41467-020-18570-x.
¡¡¡¡[36] Wolf Y,Anderson A C,Kuchroo V K.TIM3 comes of age as an inhibitory receptor[J].Nat Rev Immunol,2020,20(3):173-185.
¡¡¡¡[37] Tang R,Rangachari M,Kuchroo V K.Tim-3:A co-receptor with perse roles in T cell exhaustion and tolerance[J/OL].Semin Immunol,2019,42:101302.DOI:10.1016/j.smim.2019.101302.
¡¡¡¡[38] Zou Y,Lei W,Su S,et al.Chlamydia trachomatis plasmid-encoded protein Pgp3 inhibits apoptosis via the PI3K-AKT-mediated MDM2-p53 axis[J].Mol Cell Biochem,2019,452(1/2):167-176.
¡¡¡¡[39] Rother M,Teixeira da Costa A R,Zietlow R,et al.Modulation of host cell metabolism by Chlamydia trachomatis[J/OL].Microbiol Spectr,2019,7(3):BAI-0012-2019.DOI:10.1128/microbiolspec.BAI-0012-2019.
¡¡¡¡[40] Waguia Kontchou C,Tzivelekidis T,Gentle I E,et al.Infection of epithelial cells with Chlamydia trachomatis inhibits TNF-induced apoptosis at the level of receptor internalization while leaving non-apoptotic TNF-signalling intact[J].Cell Microbiol,2016,18(11):1583-1595.
¡¡¡¡[41] Sixt B S,Bastidas R J,Finethy R,et al.The Chlamydia trachomatis inclusion membrane protein CpoS counteracts STING-mediated cellular surveillance and suicide programs[J].Cell Host Microbe,2017,21(1):113-121.

×÷Õßµ¥Î»£ºÄÏ»ª´óѧ²¡Ô­ÉúÎïѧÑо¿Ëù
Ô­Îijö´¦£ººÎ˼ÇÛ,³Â³¬Èº,ÎâÒÆı.ÒÂÔ­Ìå³ÖÐøÐÔ¸ÐȾËÞÖ÷µÄÃâÒßÌÓÒÝ»úÖÆ[J].ϸ°ûÓë·Ö×ÓÃâÒßѧÔÓÖ¾,2021,37(05):467-473.
Ïà¹ØÄÚÈÝÍƼö
Ïà¹Ø±êÇ©£º
·µ»Ø£ºÃâÒßѧÂÛÎÄ