Roles of Salmonella enterica serovar Typhimurium encoded Peptidase N during systemic infection of Ifnγ-/- mice
Roles of Salmonella enterica serovar Typhimurium encoded Peptidase N during systemic infection of Ifnγ-/- mice
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DOI：
10.1016/j.imbio.2011.07.010
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发表时间：
2012-03-01
期刊：
影响因子：
2.8
通讯作者：
Nandi, Dipankar
中科院分区：
文献类型：
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作者：
Bhosle, Manoj;Kadthur, Jayachandra C.;Nandi, Dipankar
已知病原体编码的多肽酶在感染过程中起重要作用；然而，它们在调节免疫受损个体的宿主反应中的作用尚未得到很好的研究。鼠伤寒沙门氏菌(WT)编码的肽酶N(PepN)是一种主要的氨基肽酶，也是唯一的M1家族成员，它在缺乏干扰素-γ(干扰素-γ)的小鼠身上进行了研究。在C57BL/6小鼠全身感染过程中，缺乏PepN的鼠伤寒沙门氏菌(Delta PepN)与WT相比，外周器官的集落形成单位(CFU)增加。然而，与C57BL/6小鼠相比，干扰素γ(-/-)小鼠表现出更高的CFU，导致WT和Delta PepN之间的倍数差异较小。同时，在Delta PepN(Delta PepN/PepN)中重新引入PepN会减少CFU，表现出PepN依赖。有趣的是，一个催化失活的PepN(Delta PepN/E298A)的表达也降低了CFU，表明CPU的减少与PepN的催化活性无关。此外，在感染C57BL/6和干扰素γ(-/-)小鼠之间还观察到了三个明显的差异：第一，干扰素γ(-/-)小鼠感染后血清中肿瘤坏死因子α和白介素1β的含量显著降低。其次，对C57BL16小鼠的组织学分析表明，与Delta PepN/PepN或Delta PepN/E298A相比，WT或Delta PepN感染对小鼠脾和肝脏的损害更大。另一方面，干扰素伽马(-/-)小鼠对本研究中使用的所有鼠伤寒沙门氏菌株的器官损伤都非常敏感。最后，在感染Delta PepN/PepN或Delta PepN/E298A后，观察到C57BL/6小鼠的存活率更高，而不是干扰素γ(-/-)小鼠。总体而言，宿主编码的干扰素在感染不同毒力的鼠伤寒沙门氏菌株过程中的作用得到了强调。(C)2011年爱思唯尔股份有限公司。版权所有。
Pathogen encoded peptidases are known to be important during infection; however, their roles in modulating host responses in immunocompromised individuals are not well studied. The roles of S. typhimurium (WT) encoded Peptidase N (PepN), a major aminopeptidase and sole M1 family member, was studied in mice lacking Interferon-gamma (IFN gamma), a cytokine important for immunity. S. typhimurium lacking pepN (Delta pepN) displays enhanced colony forming units (CFU) compared to WT in peripheral organs during systemic infection in C57BL/6 mice. However, Ifn gamma(-/-) mice show higher CFU compared to C57BL/6 mice, resulting in lower fold differences between WT and Delta pepN. Concomitantly, reintroduction of pepN in Delta pepN (Delta pepN/pepN) reduces CFU, demonstrating pepN-dependence. Interestingly, expression of a catalytically inactive PepN (Delta pepN/E298A) also lowers CFU, demonstrating that the decrease in CPU is independent of the catalytic activity of PepN. In addition, three distinct differences are observed between infection of C57BL/6 and Ifn gamma(-/-) mice: First, serum amounts of TNF alpha and IL1 beta post infection are significantly lower in Ifn gamma(-/-) mice. Second, histological analysis of C57BL16 mice reveals that damage in spleen and liver upon infection with WT or Delta pepN is greater compared to Delta pepN/pepN or Delta pepN/E298A. On the other hand, Ifn gamma(-/-) mice are highly susceptible to organ damage by all strains of S. typhimurium used in this study. Finally, greater survival of C57BL/6, but not Ifn gamma(-/-) mice, is observed upon infection with Delta pepN/pepN or Delta pepN/E298A. Overall, the roles of the host encoded IFN gamma during infection with S. typhimurium strains with varying degrees of virulence are highlighted. (C) 2011 Elsevier GmbH. All rights reserved.