Department of Molecular Medicine, Jamia Hamdard, New Delhi, 110062, India.
Cellular and Molecular Immunology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
FEMS Microbiol Rev. 2023 Jan 16;47(1). doi: 10.1093/femsre/fuac041.
The intracellular viral, bacterial, or parasitic pathogens evade the host immune challenges to propagate and cause fatal diseases. The microbes overpower host immunity at various levels including during entry into host cells, phagosome formation, phagosome maturation, phagosome-lysosome fusion forming phagolysosomes, acidification of phagolysosomes, and at times after escape into the cytosol. Phagolysosome is the final organelle in the phagocyte with sophisticated mechanisms to degrade the pathogens. The immune evasion strategies by the pathogens include the arrest of host cell apoptosis, decrease in reactive oxygen species, the elevation of Th2 anti-inflammatory response, avoidance of autophagy and antigen cross-presentation pathways, and escape from phagolysosomal killing. Since the phagolysosome organelle in relation to infection/cure is seldom discussed in the literature, we summarize here the common host as well as pathogen targets manipulated or utilized by the pathogens established in phagosomes and phagolysosomes, to hijack the host immune system for their benefit. These common molecules or pathways can be broad-spectrum therapeutic targets for drug development for intervention against infectious diseases caused by different intracellular pathogens.
细胞内的病毒、细菌或寄生虫病原体逃避宿主免疫挑战以进行繁殖并导致致命疾病。微生物在多个层面上克服宿主免疫，包括进入宿主细胞、吞噬体形成、吞噬体成熟、吞噬体-溶酶体融合形成吞噬溶酶体、吞噬溶酶体酸化以及有时在逃入细胞质后。吞噬溶酶体是吞噬细胞中的最后一个细胞器，具有复杂的机制来降解病原体。病原体的免疫逃避策略包括阻止宿主细胞凋亡、减少活性氧、升高 Th2 抗炎反应、避免自噬和抗原交叉呈递途径以及逃避吞噬溶酶体杀伤。由于吞噬溶酶体细胞器与感染/治愈的关系在文献中很少讨论，我们在此总结了常见的宿主以及病原体在吞噬体和吞噬溶酶体中建立的靶点，以利用宿主免疫系统为其自身利益服务。这些常见的分子或途径可以成为广谱治疗靶点，用于开发药物以干预由不同细胞内病原体引起的传染病。
