[Research Background] Infectious diseases are responsible for nearly 20% of global mortality, with HIV, tuberculosis, malaria, and various respiratory infections being the leading causes of death. These diseases pose a significant public health burden in low-income countries, contributing to high mortality rates and prolonged health consequences. However, emerging infectious diseases are also a growing threat to high-income nations, where they not only jeopardize public health but can also disrupt economic stability. A notable example is the global COVID-19 (SARS-CoV-2) pandemic, which has triggered an unprecedented global crisis affecting society, the economy, and healthcare systems. Other high-risk infection areas also demand attention. For instance, foodborne outbreaks caused by Salmonella and enterohemorrhagic E. coli (EHEC) continue to challenge food safety; new flu virus variants with pandemic potential pose a risk of catastrophic global flu outbreaks; and the recurring Ebola virus outbreaks in Africa have had a profound impact on regional healthcare infrastructures.

[Theoretical Background and Historical Development of the Research] Pathogens and hosts have developed a complex and dynamic interplay through co-evolution. To enhance their infectivity, pathogens have evolved various mechanisms to manipulate host cell behavior. In 1996, the concept of "Cellular Microbiology" emerged as an interdisciplinary field combining molecular microbiology, which focuses on pathogens, and cell biology, which centers on host organisms. This approach has enabled scientists to explore how pathogen effectors exploit host cellular mechanisms to sustain the infection process. These investigations have not only revealed pathogen infection strategies but also illuminated fundamental cellular processes, such as cytoskeletal regulation, vesicular trafficking, cell death mechanisms, and host immune responses. These discoveries have also paved the way for the development of more effective treatments for infectious diseases.

[Mechanisms of Pathogen Invasion of Host Cells] Pathogens, including bacteria, viruses, and parasites, invade host cells via various mechanisms, such as receptor-mediated endocytosis, phagocytosis, and non-receptor-dependent fluid-phase endocytosis or micropinocytosis. Once inside the host cell, pathogens can traverse or dissolve surrounding membranes, utilizing the cytoskeleton for directed intracellular movement. During this process, host cells recognize pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs) and trigger immune responses. However, many pathogens can suppress host immune defenses using specific virulence factors, or manipulate the host cell’s membrane and molecular transport systems to optimize nutrient uptake, immune evasion, and efficient exit from the host cell. Viruses, in particular, hijack the host cell's membrane and molecular transport processes to replicate efficiently in the cytoplasmic membrane or enter the nucleus to exploit the host's genetic machinery for viral genome replication and packaging. Investigating these interaction mechanisms not only reveals the adaptability of host cell regulation but also provides critical insights for designing innovative therapeutic strategies.

[Research Tools and Methods] To comprehensively analyze the interactions between pathogens and host cells, we employ cutting-edge computational biology tools and bioinformatics software. These advanced tools allow us to process complex biological data, including DNA, RNA, single-cell RNA sequencing data, epigenomics, proteomics, and metabolomics, providing vital insights into the biological mechanisms of pathogens. By leveraging our self-developed computational tools and the latest bioinformatics methods, we are able to conduct efficient data analysis and drive the development of novel therapies, offering substantial technical support for optimizing treatment strategies.

【研究背景】传染病约占全球死亡人数的20%，其中HIV感染、结核病、疟疾和各类呼吸道感染是主要致死原因。这些疾病对低收入国家造成了极大的公共卫生负担，使其面临严重的死亡率和长期的健康损失。然而，新兴传染病同样对高收入国家构成显著威胁，不仅可能危及公共卫生安全，还可能对经济稳定造成深远影响。席卷全球的新冠病毒（SARS-CoV-2）大流行便是一个典型的例子，其引发了全球范围内前所未有的社会、经济和卫生危机。此外，其他高风险的感染领域也值得关注。例如，由沙门氏菌和肠出血性大肠杆菌（EHEC）引起的食源性疫情多次爆发，对食品安全构成挑战；具有全球传播潜力的新型流感病毒变种，可能引发灾难性流感疫情；以及非洲地区反复暴发的埃博拉病毒疫情，其对区域卫生系统的冲击尤为显著。

【研究的理论背景和历史发展】病原体与宿主在共同演化过程中形成了一种微妙而复杂的动态博弈。为了优化感染能力，病原体发展出了多种机制来操控宿主细胞的行为。1996年，“细胞微生物学”（Cellular Microbiology）这一概念首次提出，它代表了一门新兴的交叉学科，融合了分子微生物学（以研究病原体为核心）和细胞生物学（以研究宿主为核心）的研究方法。通过这一视角，科学家们深入探讨了病原体效应器如何利用宿主细胞的分子机制以维持感染过程。这些研究不仅揭示了病原体感染的策略，还阐明了细胞生物学的基本原理，例如细胞骨架调控、囊泡运输、细胞死亡机制和宿主防御反应等。同时，这些发现推动了更有效的传染病治疗方案的开发。

【病原体入侵宿主细胞的机制】细菌、病毒和寄生虫等病原体通过多种宿主细胞摄取机制侵入细胞，这些机制主要包括受体介导的内吞作用和吞噬作用，此外还包括非受体依赖的胞饮作用和微胞饮作用等途径。一旦进入宿主细胞，病原体能够穿越或溶解其周围的膜，借助细胞骨架实现细胞内的定向运动。在这一过程中，宿主细胞通过模式识别受体（PRRs）识别病原体相关分子模式（PAMPs），并激活免疫应答。然而，许多病原体可以通过特定的毒力因子抑制宿主的免疫反应，或者通过操控宿主细胞的膜和分子运输系统，优化对营养物质的获取、免疫逃避以及从宿主细胞的排出效率。病毒则通过劫持宿主细胞内的膜和分子运输过程，在胞质膜结构中高效复制，或者进入细胞核以利用宿主的遗传机制进行病毒基因组的复制和包装。对这些相互作用机制的研究不仅揭示了宿主细胞调控的灵活性，也为新疗法的设计提供了独特的视角。

【研究工具与方法】为了深入分析病原体与宿主细胞的相互作用，我们采用了最先进的计算生物学工具和生物信息学软件。这些工具能够处理复杂的生物数据，包括DNA、RNA、单细胞RNA测序数据、表观基因组、蛋白质组和代谢组等，为揭示病原体的生物学机制提供了重要支持。通过 自主开发的计算生物学工具 和 最新的生物信息学分析方法，我们能够高效地分析数据，并推动新疗法的开发与创新，为治疗方案的优化提供有力的技术支持。