Significant Growth by Rickettsia Species within Human Macrophage-Like Cells Is a Phenotype Correlated with the Ability to Cause Disease in Mammals.
Significant Growth by Rickettsia Species within Human Macrophage-Like Cells Is a Phenotype Correlated with the Ability to Cause Disease in Mammals.
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DOI：
10.3390/pathogens10020228
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发表时间：
2021-02-19
期刊：
影响因子：
--
通讯作者：
Martinez JJ
中科院分区：
文献类型：
--
作者：
Kristof MN;Allen PE;Yutzy LD;Thibodaux B;Paddock CD;Martinez JJ
立克次体是全球人类蜱传疾病的重要来源。在北美，斑点热群立克次体中的两个物种已被确定与人类疾病有关：立克次体立克次体，落基山斑点热的病原体，和立克次体帕克氏体，R.帕克氏立克次体病我们实验室以前的工作表明，在THP-1衍生的巨噬细胞内，另一种致病性SFG立克次体物种，康氏立克次体的非内皮寄生，我们假设这种生长特征可能是哺乳动物宿主立克次体发病机制的一个未被充分认识的方面。在这项工作中，我们证明了多种其他公认的人类致病性立克次体，包括R。rickettsii，R.帕克氏立克次体、非洲立克次体和赤立立克次体可以在靶内皮细胞内以及PMA分化的THP-1细胞内生长。与此相反，贝氏立克次体，一种与人类疾病无关的立克次体，和R。立克次体爱荷华州株是致病性立克次体的无毒衍生株。立克次氏体可侵入两种细胞类型，但仅在内皮细胞内增殖。进一步的分析表明，类似于以前的研究R。conorii，其他公认的致病性立克次体物种可以在THP-1衍生的巨噬细胞的胞质溶胶内生长，并且避免了与溶酶体区室的两种不同标记物（LAMP-2和组织蛋白酶D）的定位。R.另一方面，bellii显示出与溶酶体区室的显著共定位。总的来说，这些发现表明致病性立克次体物种在巨噬细胞样细胞内建立生态位的能力可能是其在哺乳动物中引起疾病的能力的重要因素。这些研究结果还表明，哺乳动物吞噬细胞内的生长分析可能有助于预测新分离和鉴定的立克次体种的致病潜力。
Rickettsia are significant sources of tick-borne diseases in humans worldwide. In North America, two species in the spotted fever group of Rickettsia have been conclusively associated with disease of humans: Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, and Rickettsia parkeri, the cause of R. parkeri rickettsiosis. Previous work in our lab demonstrated non-endothelial parasitism by another pathogenic SFG Rickettsia species, Rickettsia conorii, within THP-1-derived macrophages, and we have hypothesized that this growth characteristic may be an underappreciated aspect of rickettsial pathogenesis in mammalian hosts. In this work, we demonstrated that multiple other recognized human pathogenic species of Rickettsia, including R. rickettsii, R. parkeri, Rickettsia africae, and Rickettsia akari can grow within target endothelial cells as well as within PMA-differentiated THP-1 cells. In contrast, Rickettsia bellii, a Rickettsia species not associated with disease of humans, and R. rickettsii strain Iowa, an avirulent derivative of pathogenic R. rickettsii, could invade both cell types but proliferate only within endothelial cells. Further analysis revealed that similar to previous studies on R. conorii, other recognized pathogenic Rickettsia species could grow within the cytosol of THP-1-derived macrophages and avoided localization with two different markers of lysosomal compartments; LAMP-2 and cathepsin D. R. bellii, on the other hand, demonstrated significant co-localization with lysosomal compartments. Collectively, these findings suggest that the ability of pathogenic rickettsial species to establish a niche within macrophage-like cells could be an important factor in their ability to cause disease in mammals. These findings also suggest that analysis of growth within mammalian phagocytic cells may be useful to predict the pathogenic potential of newly isolated and identified Rickettsia species.
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影响因子：
3.7
作者：
Gillespie, Joseph J.;Williams, Kelly;Shukla, Maulik;Snyder, Eric E.;Nordberg, Eric K.;Ceraul, Shane M.;Dharmanolla, Chitti;Rainey, Daphne;Soneja, Jeetendra;Shallom, Joshua M.;Vishnubhat, Nataraj Dongre;Wattam, Rebecca;Purkayastha, Anjan;Czar, Michael;Crasta, Oswald;Setubal, Joao C.;Azad, Abdu F.;Sobral, Bruno S.
通讯作者：
Sobral, Bruno S.
影响因子：
3.4
作者：
Cardwell MM;Martinez JJ
通讯作者：
Martinez JJ
影响因子：
6.4
作者：
Lehman, Stephanie S.;Noriea, Nicholas F.;Hackstadt, Ted
通讯作者：
Hackstadt, Ted
影响因子：
2.1
作者：
Hecht, Joy A.;Allerdice, Michelle E. J.;Karpathy, Sandor E.
通讯作者：
Karpathy, Sandor E.
影响因子：
21.3
作者：
Haglund CM;Choe JE;Skau CT;Kovar DR;Welch MD
通讯作者：
Welch MD