表达鼠干扰素λ3（MuIFNλ3）的重组LAB载体对甲型流感病毒（IAV）感染的免疫辅助潜力。

IF 4.3 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut Pathogens Pub Date : 2023-10-30 DOI:10.1186/s13099-023-00578-5

Sandeep Yadav, Aparna Varma, Aparna Odayil Muralidharan, Sucharita Bhowmick, Samiran Mondal, Amirul Islam Mallick

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引用次数: 0

摘要

背景：控制A型流感病毒（IAV）感染复发性流行病的传统方法仍然具有挑战性，主要是因为其高度变异性和耐药性增加。作为控制IAV感染的一种替代方案，预防性使用细胞因子来驱动多种抗病毒宿主因子的免疫激活已被逐渐认识到。其中，III型干扰素（IFN）通过上调几种抗病毒基因的表达，包括特异性靶向病毒复制机制的干扰素刺激基因（ISG），在诱导强效抗病毒宿主反应中发挥着关键作用。为了利用免疫辅助潜力，我们检测了IFNλ3（一种III型IFN）的预处理是否可以激活抗病毒宿主对IAV感染的反应。方法：在本研究中，我们对食品级乳酸生产菌乳酸乳球菌（L.lactis）进行生物工程设计，在细胞外环境中表达和分泌功能性小鼠IFNλ3（MuIFNλ）蛋白。为了测试重组乳杆菌（rL.lactis）分泌的MuIFNλ3的免疫保护潜力，我们使用小鼠B16F10细胞作为体外模型，而小鼠（BALB/c）用于体内研究。结果：我们的研究表明，用rL分泌的MuIFNλ3启动。乳糖可以上调几种抗病毒基因的表达，包括干扰素调节因子（IRFs）和ISGs，而不会加剧肺部或肠道炎症反应。此外，我们还表明，用MuIFNλ3预处理B16F10细胞可以对小鼠适应的流感病毒A/PR/8/1934（H1N1）感染提供显著的免疫保护。结论：由于IAV感染的主要靶点是上呼吸道和胃肠道，在不影响组织稳态的情况下进行免疫激活表明IFNλ3对IAV感染具有免疫辅助潜力。

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The immune-adjunctive potential of recombinant LAB vector expressing murine IFNλ3 (MuIFNλ3) against Type A Influenza Virus (IAV) infection.

Background: The conventional means of controlling the recurring pandemics of Type A Influenza Virus (IAV) infections remain challenging primarily because of its high mutability and increasing drug resistance. As an alternative to control IAV infections, the prophylactic use of cytokines to drive immune activation of multiple antiviral host factors has been progressively recognized. Among them, Type III Interferons (IFNs) exhibit a pivotal role in inducing potent antiviral host responses by upregulating the expression of several antiviral genes, including the Interferon-Stimulated Genes (ISGs) that specifically target the virus replication machinery. To harness the immuno-adjunctive potential, we examined whether pre-treatment of IFNλ3, a Type III IFN, can activate antiviral host responses against IAV infections.

Methods: In the present study, we bioengineered a food-grade lactic acid-producing bacteria (LAB), Lactococcus lactis (L. lactis), to express and secrete functional murine IFNλ3 (MuIFNλ3) protein in the extracellular milieu. To test the immune-protective potential of MuIFNλ3 secreted by recombinant L. lactis (rL. lactis), we used murine B16F10 cells as an in vitro model while mice (BALB/c) were used for in vivo studies.

Results: Our study demonstrated that priming with MuIFNλ3 secreted by rL. lactis could upregulate the expression of several antiviral genes, including Interferon Regulatory Factors (IRFs) and ISGs, without exacerbated pulmonary or intestinal inflammatory responses. Moreover, we also showed that pre-treatment of B16F10 cells with MuIFNλ3 can confer marked immune protection against mice-adapted influenza virus, A/PR/8/1934 (H1N1) infection.

Conclusion: Since the primary target for IAV infections is the upper respiratory and gastrointestinal tract, immune activation without affecting the tissue homeostasis suggests the immune-adjunctive potential of IFNλ3 against IAV infections.

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来源期刊

Gut Pathogens GASTROENTEROLOGY & HEPATOLOGY-MICROBIOLOGY

CiteScore

7.70

自引率

2.40%

发文量

期刊介绍： Gut Pathogens is a fast publishing, inclusive and prominent international journal which recognizes the need for a publishing platform uniquely tailored to reflect the full breadth of research in the biology and medicine of pathogens, commensals and functional microbiota of the gut. The journal publishes basic, clinical and cutting-edge research on all aspects of the above mentioned organisms including probiotic bacteria and yeasts and their products. The scope also covers the related ecology, molecular genetics, physiology and epidemiology of these microbes. The journal actively invites timely reports on the novel aspects of genomics, metagenomics, microbiota profiling and systems biology. Gut Pathogens will also consider, at the discretion of the editors, descriptive studies identifying a new genome sequence of a gut microbe or a series of related microbes (such as those obtained from new hosts, niches, settings, outbreaks and epidemics) and those obtained from single or multiple hosts at one or different time points (chronological evolution).