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Salmonella-Driven Polarization of Granuloma Macrophages Antagonizes TNF-Mediated Pathogen Restriction during Persistent Infection'ÀÔ´Ï´Ù.
Granuloma´Â ¿©·¯ inflammatory cellsÀÇ ÁýÇÕü·Î, persistent stimuli¿¡ ¹ÝÀÀÇÏ¿© antigen disseminationÀ» ¸·´Â host protectiveÇÑ ¿ªÇÒÀ» ¼öÇàÇÕ´Ï´Ù. ¹Ý´ë·Î, granuloma¸¦ ±¸¼ºÇÏ´Â macrophageÀÇ Æ¯¼º¿¡ µû¶ó, bacteria persistence¸¦ À§ÇÑ cellular niche¸¦ Á¦°øÇÏ´Â µî intracellular bacterial pathogens beneficialÇÑ ¿ªÇÒÀ» ¼öÇàÇÒ ¼ö ÀÖ½À´Ï´Ù.
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Salmonella Typhimurium (STm) °¨¿° ½Ã¿¡ granuloma macrophage polarization¿Í pathogen persistenceÀÇ °ü°è¸¦ TNF signaling ¹× STm SteE¸¦ ÅëÇØ È®ÀÎÇß½À´Ï´Ù. °á°úÀûÀ¸·Î, TNF signalingÀÌ M2 granuloma macrophage polarizationÀ» Á¦ÇÑÇÔÀ¸·Î½á pathogen persistence¸¦ ¾ïÁ¦ÇÏ°í, STm SteE´Â M2 granuloma macrophage polarizationÀ» ÃËÁøÇÔÀ¸·Î½á TNF-mediated restrictionÀ» ±Øº¹ÇÑ´Ù´Â °ÍÀ» ¹àÇû½À´Ï´Ù.
¸ÕÀú, STm °¨¿° ½Ã¿¡ granuloma macrophage ¼ö°¡ Áõ°¡ÇÏ°í antimicrobial response¿¡ µû¶ó TNF ¿Í iNOS productionÀÌ Áõ°¡ÇÔÀ» È®ÀÎ Çß½À´Ï´Ù. ¶ÇÇÑ, M2 macrophage markerÀÎ CD301À» ÅëÇØ granuloma periphery À§Ä¡¿¡ CD301 positive populationÀ» È®ÀÎÇß°í À̵éÀÇ antimicrobial functionsÀÌ »ó´ëÀûÀ¸·Î ³·´Ù´Â °ÍÀ» È®ÀÎÇß½À´Ï´Ù.
´ÙÀ½À¸·Î, TNF neutralization ½Ã¿¡ granuloma macrophageÀÇ IL-4Rα expression, CD301 positive population, ±×¸®°í bacterial burdenÀÌ Áõ°¡ÇÏ´Â °ÍÀ» ÅëÇØ TNF signalingÀÌ M2 granuloma macrophage polarizationÀ» ¾ïÁ¦ÇÔÀ» È®ÀÎÇß°í, SteE mutant STm °¨¿° ½Ã¿¡´Â ÇØ´ç ¿äÀεéÀÌ °¨¼ÒÇÏ´Â °ÍÀ» ÅëÇØ STm SteE¸¦ ¸Å°³·Î M2 granuloma macrophage polarizationÀÌ À¯µµµÊÀ» È®ÀÎÇß½À´Ï´Ù.
À̸¦ ÅëÇØ STmÀÌ M2-like features·ÎÀÇ state º¯È¸¦ À¯µµÇØ granuloma macrophage ³»¿¡¼ persistent haborÇϸç, ÀÌ¿Í °ü·ÃÇÑ TNF ¹× SteEÀÇ ¹Ý´ëµÇ´Â ÀÛ¿ëÀ» ÅëÇØ macrophage polarizationÀ» Á¶ÀýÇÏ´Â °ÍÀÌ intracellular bacteria¿¡ ´ëÇ×ÇÏ´Â ÇϳªÀÇ Àü·«ÀÌ µÉ ¼ö ÀÖÀ½À» º¸¿©ÁÖ°í ÀÖ½À´Ï´Ù.
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https://www.sciencedirect.com/science/article/pii/S1931312819305931?via%3Dihub#bib34