Mycobacterium abscessus ESX-3 plays an important role in host inflammatory and pathological responses during infection

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• 作者：Yi Sak Kim^a ; ^c ; ¹ ; Chul-Su Yang^d ; ¹ ; Loi T. Nguyen^e ; Jin Kyung Kim^a ; ^c ; Hyo Sun Jin^a ; ^c ; Jin ho Choe^a ; ^c ; Soo Yeon Kim^a ; ^c ; Hye-Mi Lee^a ; ^c ; Mingyu Jung^b ; ^c ; Jin-Man Kim^b ; ^c ; Myung Hee Kim^e ; Eun-Kyeong Jo^a ; ^c ; Ji-Chan Jang^a ; ^c ; ^f ; ^{jichanjang@gnu.ac.kr}
• 关键词：Mycobacterium abscessus ; ESX-3 ; Host inflammation
• 刊名：Microbes and Infection
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：19
• 期：1
• 页码：5-17
• 全文大小：3411 K
• 卷排序：19

文摘

Mycobacterial ESX systems are often related to pathogenesis during infection. However, little is known about the function of ESX systems of Mycobacterium abscessus (Mab). This study focuses on the Mab ESX-3 cluster, which contains major genes such as esxH (Rv0288, low molecular weight protein antigen 7; CFP-7) and esxG (Rv0287, ESAT-6 like protein). An esx-3 (MAB 2224c-2234c)-deletional mutant of Mab (Δesx) was constructed and used to infect murine and human macrophages. We then investigated whether Mab Δesx modulated innate host immune responses in macrophages. Mab Δesx infection resulted in less pathological and inflammatory responses. Additionally, Δesx resulted in significantly decreased activation of inflammatory signaling and cytokine production in macrophages compared to WT. Moreover, recombinant EsxG·EsxH (rEsxGH) proteins encoded by the ESX-3 region showed synergistic enhancement of inflammatory cytokine generation in macrophages infected with Δesx. Taken together, our data suggest that Mab ESX-3 plays an important role in inflammatory and pathological responses during Mab infection.