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Á¦°¡ À̹ø¿¡ ¼±Á¤ÇÑ ³í¹®Àº 2023³â 8¿ù nature commuinications¿¡ ÃâÆÇµÈ ‘Toll-like receptor 4 and macrophage scavenger receptor 1 crosstalk regulates phagocytosis of a fungal pathogen’ ÀÔ´Ï´Ù.
Cryptococcus neoformans´Â Æó·Î °¨¿°µÇ´Â º´¿øü·Î °¨¿°½Ã »ç¸ÁÀ» ÀÏÀ¸Å³ ¼ö ÀÖ½À´Ï´Ù. non-opsonized cryptococci´Â phagocytose capacity°¡ ÁÙ¾îµéÁö¸¸ Æó¿¡´Â opsonin antibody°¡ Àû¾î¼ ³·Àº levelÀÇ non-opsonic phagocytosisµµ Áß¿äÇÕ´Ï´Ù.
ÀÌ·¯ÇÑ non-opsonic phagocytosis´Â PRR¿¡ ÀÇÇÑ PAMPÀνĿ¡ ÀÇÇØ ½ÃÀ۵Ǵµ¥ PRRÁß ÇϳªÀÎ TLR4´Â fungiÀÇ ¼ººÐÀ» ÀνÄÇÏ´Â °ÍÀ¸·Î Àß ¾Ë·ÁÁ® ÀÖ½À´Ï´Ù.
ÀÌ¿¡ º» ³í¹®Àº TLR4ÀÇ Cryptococcus neoformans·ÎÀÇ ÀÛ¿ëÀ» »ìÆ캸±â À§ÇØ TLR4 knockout ¶Ç´Â TLR4 inhibitÀ» ÇÏ¿´´Âµ¥, ¿ÀÈ÷·Á Cryptococcus neoformans¿¡ ´ëÇÑ non-opsonic phagocytosis°¡ Áõ°¡ÇÔÀ» °üÂûÇÏ¿´½À´Ï´Ù.
±× ÈÄ ±âÁ¸¿¡ ¾Ë·ÁÁø TLR4ÀÇ ÀÛ¿ëÀÌ Á¦ÇÑµÈ »óȲ¿¡¼ ¿©·¯ scavenger receptorÀÇ ¹ßÇöÀÌ Áõ°¡ÇÑ´Ù´Â »ç½ÇÀ» ¹ÙÅÁÀ¸·Î ÀÌ Çö»óÀÌ scavenger receptor¿Í °ü·ÃÀÌ ÀÖ´ÂÁö »ìÆ캸±â À§ÇØ scavenger receptorÀÇ competitive inhibitorÀÎ ox-LDLÀ» ó¸®ÇÏ¿´½À´Ï´Ù.
ÇØ´ç °á°ú´Â Cryptococcus neoformans¿¡ ´ëÇÑ non-opsonic phagocytosis°¡ °¨¼ÒÇÔÀ» °üÂûÇÏ¿´½À´Ï´Ù.
ÀÌ¿¡ ±â¿©ÇÏ´Â ÁÖ¿äÇÑ scavenger receptor¸¦ ¾Ë¾Æ³»±â À§ÇØ flow cytometry·Î receptorµéÀÇ surface expressionÀ» ÃøÁ¤ÇÑ °á°ú, MSR1ÀÇ ¹ßÇöÀÌ TLR4 knockout½Ã¿¡ ´Þ¶óÁø °ÍÀ» È®ÀÎÇÏ¿´½À´Ï´Ù.
¶Ç, Ãß°¡·Î Cryptococcus neoformans·ÎÀÇ ¹ÝÀÀÀº TLR4 »Ó¸¸ ¾Æ´Ï¶ó TLR2, TLR3, TLR9µµ °ü¿©ÇÏ´Â °ÍÀÌ ¾Ë·ÁÁ® ÀÖ¾ú´Âµ¥ ´Ù¸¥ TLRµµ °ü·ÃÀÌ ÀÖ´ÂÁö ¾Ë¾Æº¸±â À§ÇØ °¢°¢ÀÇ TLR¿¡ inhibitorµéÀ» ó¸®ÇÏ¿´½À´Ï´Ù. ±× °á°ú, TLR3 inhibitor 󸮽ÿ¡ TLR4 knockoutÀ¸·Î Áõ°¡ÇÑ non-opsonic phagocytosis°¡ °¨¼ÒÇÏ¿´°í TLR3µµ ¿¬°üÀÌ ÀÖÀ½À» ¹ß°ßÇÏ¿´½À´Ï´Ù.
¸¶Áö¸·À¸·Î, ÀÌ·¯ÇÑ mechanismÀÌ TLR4¿Í TLR3ÀÇ ÇÏÀ§ ½Ã±×³ÎÀÎ MyD88¿Í TRIF signallingÀ¸·Î ÀÎÇÑ °ÍÀÓÀ» ¹àÇô³ÂÀ¸¸ç Ãß°¡·Î TLR4 knockout½Ã¿¡ ÀÌ·¯ÇÑ Çö»óÀÌ FcγRs, SYK, PI3K, ERK1/2, p38°úµµ ¿¬°üÀÌ ÀÖÀ½À» ¹àÇô³Â½À´Ï´Ù.
À§ ³í¹®À» ¼±Á¤ÇÑ ÀÌÀ¯´Â HD11 TLR knockout ½ÇÇèÀ» ÁغñÇϴµ¥ ÀÖ¾î¼, TLR3¿Í TLR4ÀÇ crosstalk, ±×¸®°í TLR knockout½Ã¿¡ ´Ù¸¥ PRRÀÇ compensatory response °¡´É¼ºÀ» °øºÎÇÏ°í, ±×·¯ÇÑ ½ÇÇèÀÇ schemeÀ» °øºÎÇϱâ À§ÇÏ¿© ¼±Á¤ÇÏ¿´½À´Ï´Ù.
¿½ÉÈ÷ ÁغñÇÏ¿© Åä¿äÀÏ¿¡ ºË°Ú½À´Ï´Ù.
³í¹® ¸µÅ© : https://www.nature.com/articles/s41467-023-40635-w