Dynamic reorganization of the actin cytoskeleton dictates plasma membrane morphology and is frequently subverted by bacterial pathogens for entry and colonization of host cells. The human-adapted bacterial pathogen Neisseria gonorrhoeae can colonize and replicate when cultured with human macrophages, however the basic understanding of how this process occurs is incomplete. N. gonorrhoeae is the etiological agent of the sexually transmitted disease gonorrhea and tissue resident macrophages are present in the urogenital mucosa which is colonized by the bacteria. We uncovered that when gonococci colonize macrophages they can establish an intracellular or a cell surface-associated niche that support bacterial replication independently. Unlike other intracellular bacterial pathogens, which enter host cells as single bacterium, establish an intracellular niche and then replicate, gonococci invade human macrophages as a colony. Individual diplococci are rapidly phagocytosed by macrophages and transported to lysosomes for degradation. However, we found that surface-associated gonococcal colonies of various sizes can invade macrophages by triggering actin skeleton rearrangement resulting in plasma membrane invaginations that slowly engulf the colony. The resulting intracellular membrane-bound organelle supports robust bacterial replication. The gonococci-occupied vacuoles evaded fusion with the endosomal compartment and were enveloped by a network of actin filaments. We demonstrate that gonococcal colonies invade macrophages via a process mechanistically distinct from phagocytosis that is regulated by the actin nucleating factor FMNL3. Our work provides insights into the gonococci life-cycle in association with human macrophages and defines key host determinants for macrophage colonization.

中文翻译：

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淋病奈瑟氏球菌破坏了依赖于形式蛋白的肌动蛋白聚合，从而定居于人类巨噬细胞

肌动蛋白细胞骨架的动态重组决定了质膜的形态，并经常被细菌病原体所破坏，从而进入宿主细胞并在宿主细胞中定殖。当与人类巨噬细胞一起培养时，适应人类的细菌病原体淋病奈瑟氏球菌可以定殖并复制，但是对这一过程如何发生的基本了解还不完整。淋病奈瑟菌它是性病淋病的病原体，组织定居巨噬细胞存在于被细菌定殖的泌尿生殖道粘膜中。我们发现，当淋球菌定居于巨噬细胞时，它们可以建立细胞内或细胞表面相关的生态位，从而独立地支持细菌复制。不同于其他细胞内细菌病原体，它们作为单一细菌进入宿主细胞，建立细胞内生态位，然后复制，而淋球菌则侵入人类巨噬细胞作为菌落。个别双球菌迅速被巨噬细胞吞噬并转运至溶酶体进行降解。然而，我们发现，各种大小的与表面相关的淋球菌菌落都可以通过触发肌动蛋白骨架重排而侵入巨噬细胞，从而导致质膜内陷，从而慢慢吞噬菌落。所得的细胞内膜结合细胞器支持强大的细菌复制。淋球菌占据的空泡逃避了与内体区室的融合，并被肌动蛋白丝网络包裹。我们证明淋病球菌菌落通过一个过程从机械上不同于由肌动蛋白成核因子FMNL3调节吞噬作用的过程侵入巨噬细胞。我们的工作提供了与人类巨噬细胞相关的淋球菌生命周期的见解，并定义了巨噬细胞定殖的关键宿主决定因素。所得的细胞内膜结合细胞器支持强大的细菌复制。淋球菌占据的空泡逃避了与内体区室的融合，并被肌动蛋白丝网络包裹。我们证明淋病球菌菌落通过一个过程从机械上不同于由肌动蛋白成核因子FMNL3调节吞噬作用的过程侵入巨噬细胞。我们的工作提供了与人类巨噬细胞相关的淋球菌生命周期的见解，并定义了巨噬细胞定殖的关键宿主决定因素。产生的细胞内膜结合细胞器支持强大的细菌复制。淋球菌占据的空泡逃避了与内体区室的融合，并被肌动蛋白丝网络包裹。我们证明淋病球菌菌落通过一个过程从机械上不同于由肌动蛋白成核因子FMNL3调节吞噬作用的过程侵入巨噬细胞。我们的工作提供了与人类巨噬细胞相关的淋球菌生命周期的见解，并定义了巨噬细胞定殖的关键宿主决定因素。