Autophagy facilitates intracellular survival of pathogenic rickettsiae in macrophages via evasion of autophagosomal maturation and reduction of microbicidal pro-inflammatory IL-1 cytokine responses.
Autophagy facilitates intracellular survival of pathogenic rickettsiae in macrophages via evasion of autophagosomal maturation and reduction of microbicidal pro-inflammatory IL-1 cytokine responses.
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DOI：
10.1128/spectrum.02791-23
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发表时间：
2023-12-12
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
立克属由多种节肢动物和脊椎动物宿主的强制性细胞内细菌寄生虫组成。一些立克物种（spp。）在全球范围内负责严重的人类疾病。这些隐秘的病原体群体的一个有趣特征是，它们能够利用宿主对其利益的胞质防御反应的能力。然而，病原性立克属属的确切机制。埃德宿主免疫防御反应仍有待确定。在这里，我们观察到致病性的立克西亚Typhi和Rickettsia Rickettsii（Sheila Smith [SS]），但没有非致病的人力体蒙塔尼斯人在进入骨髓骨髓的巨摩托巨噬细胞后变得普遍存在并诱导自噬。此外，与蒙塔尼斯（R. Montanensis）不同，R. typhi和R. rickettsii（SS）都与LC3B共定位，而在宿主细胞进入时与LAMP2共定位。最后，我们观察到，鼠伤寒红杆菌和R. rickettsii，但不是Montanensis，都可以减少促炎性介绍性白介素-1（IL-1）细胞因子反应，这可能是通过自噬介导的机制。 In summary, we identified a previously unappreciated pathway by which both pathogenic R. typhi and R. rickettsii (SS), but not the non-pathogenic R. montanensis, become ubiquitinated, induce autophagy, avoid autolysosomal destruction, and reduce microbicidal IL-1 cytokine responses to establish an intracytosolic niche in macrophages.
立克属。是各种节肢动物和脊椎动物宿主的细胞内细菌寄生虫。一些人力体是全球多种严重的人类疾病的原因。这些病原体的一个有趣特征是它们可以利用宿主对其益处的胞质防御反应的能力。然而，病原性立克属属的确切机制。逃避的主持人防御反应尚不清楚。在这里，我们观察到致病性的立克西亚Typhi和Rickettsia Rickettsii（Sheila Smith [SS]），但没有非致病的人力体蒙塔尼斯人在进入巨噬细胞时变得泛滥并诱导自噬。此外，与蒙塔尼斯（R.最后，我们观察到，鼠伤寒和瑞克氏菌（SS），但不是蒙塔尼斯河，降低了促炎性白介素-1（IL-1）的反应，这可能是通过自噬介导的机制的。总而言之，我们确定了一种先前未欣赏的途径，通过该途径，致病性孢子虫和瑞克氏菌（SS）均被泛素化，诱导自噬，避免自噬，避免自噬，并减少杀伤性IL-1细胞因子反应，以建立巨噬细胞内的内菌果实。
The genus Rickettsia is comprised of obligate intracellular bacterial parasites of a wide range of arthropod and vertebrate hosts. Some Rickettsia species (spp.) are responsible for serious human diseases globally. One interesting feature of these stealthy group of pathogens is their ability to exploit host cytosolic defense responses to their benefits. However, the precise mechanism by which pathogenic Rickettsia spp. elude host immune defense responses remains to be determined. Here, we observed that pathogenic Rickettsia typhi and Rickettsia rickettsii (Sheila Smith [SS]), but not non-pathogenic Rickettsia montanensis, become ubiquitinated and induce autophagy upon entry into bone marrow-derived macrophages. Moreover, unlike R. montanensis, both R. typhi and R. rickettsii (SS) colocalized with LC3B and not with Lamp2 upon host cell entry. Finally, we observed that both R. typhi and R. rickettsii, but not R. montanensis, reduce pro-inflammatory interleukin-1 (IL-1) cytokine responses, likely via an autophagy-mediated mechanism. In summary, we identified a previously unappreciated pathway by which both pathogenic R. typhi and R. rickettsii (SS), but not the non-pathogenic R. montanensis, become ubiquitinated, induce autophagy, avoid autolysosomal destruction, and reduce microbicidal IL-1 cytokine responses to establish an intracytosolic niche in macrophages. Rickettsia spp. are intracellular bacterial parasites of a wide range of arthropod and vertebrate hosts. Some rickettsiae are responsible for several severe human diseases globally. One interesting feature of these pathogens is their ability to exploit host cytosolic defense responses to their benefits. However, the precise mechanism by which pathogenic Rickettsia spp. elude host defense responses remains unclear. Here, we observed that pathogenic Rickettsia typhi and Rickettsia rickettsii (Sheila Smith [SS]), but not non-pathogenic Rickettsia montanensis, become ubiquitinated and induce autophagy upon entry into macrophages. Moreover, unlike R. montanensis, R. typhi and R. rickettsii (SS) colocalized with LC3B but not with Lamp2 upon host cell entry. Finally, we observed that both R. typhi and R. rickettsii (SS), but not R. montanensis, reduce pro-inflammatory interleukin-1 (IL-1) responses, likely via an autophagy-mediated mechanism. In summary, we identified a previously unappreciated pathway by which both pathogenic R. typhi and R. rickettsii (SS) become ubiquitinated, induce autophagy, avoid autolysosomal destruction, and reduce microbicidal IL-1 cytokine responses to establish an intracytosolic niche in macrophages.
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