Recent excitement regarding immune clearance of intracellular microorganisms has focused on two systems that maintain cellular homeostasis. One system includes cellular autophagy components that mediate degradation of pathogens in membrane-bound compartments, in a process termed xenophagy. The second system is driven by interferon-regulated GTPases that promote rupture of pathogen-containing vacuoles and microbial degradation. In the case of xenophagy, pathogen sequestration and compartmentalization suppress inflammation. In contrast, interferon-driven events can lead to exposure of pathogen-associated molecular patterns to the host cytosol with consequent inflammasome activation. Paradoxically, signals and factors involved in xenophagy also mobilize interferon-regulated GTPases, which drive the inflammatory response, indicating considerable cross-talk between these pathways. How these responses are prioritized remains to be understood. In this review, we describe mechanisms of intracellular pathogen clearance that rely on the autophagy machinery and interferon-regulated GTPases, and speculate how these pathways engage each other to balance pathogen elimination with inflammation.

最近关于细胞内微生物免疫清除的兴奋集中在维持细胞稳态的两个系统上。一个系统包括细胞自噬成分，这些成分介导膜结合区室中病原体的降解，这一过程称为异体自噬。第二个系统由干扰素调节的 GTP 酶驱动，这些 GTP 酶促进含有病原体的液泡破裂和微生物降解。在异种吞噬的情况下，病原体隔离和区室化可抑制炎症。相反，干扰素驱动的事件可导致病原体相关分子模式暴露于宿主细胞质溶胶，从而激活炎症小体。矛盾的是，与异食有关的信号和因素也会动员干扰素调节的 GTP 酶，从而驱动炎症反应，表明这些途径之间存在相当大的串扰。这些响应的优先级如何仍有待理解。在这篇综述中，我们描述了依赖自噬机制和干扰素调节的 GTP 酶的细胞内病原体清除机制，并推测这些途径如何相互结合以平衡病原体消除与炎症。