Srivastava Ruchi, Karan Sweta, Lekbach Yassir, Quadiri Afshana, Tohidian Ava, Maurya Chhaya, Ng Sarah Xue Le, Chow Reilly, Garcia America, Agrawal Anshu, Vahed Hawa, Chentoufi Aziz A, BenMohamed Lbachir
Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA.
Division of Basic and Clinical Immunology, Department of Medicine, University of California Irvine, Irvine, CA 92697-4375, USA.
Pathogens. 2025 Jun 23;14(7):624. doi: 10.3390/pathogens14070624.
Immune function declines with age, leading to increased vulnerability of the elderly to viral infectious pathogens. The mechanisms by which aging negatively impacts the innate and adaptive immune system, leading to enhanced susceptibility to respiratory viral pathogens, remain incompletely understood. In the present study, we utilized a mouse model of infection with herpes simplex virus type 1 (HSV-1), a virus that can infect the lungs and lead to pneumonia, a rare but serious health concern in the elderly. Following intranasal inoculation of young (6 weeks), adult (36 weeks), and aged mice (68 weeks) with HSV-1 (KOS strain) we: (i) compared the local and systemic immune responses to infection in young, adult, and aged mice, and (ii) correlated the level and type of immune responses to protection against HSV-1 infection and disease. Compared to young and adult mice, aged mice displayed: (i) increased activation of epithelial cells with a decreased expression of TLR3; (ii) increased activation of dendritic cells with increased expression of MHC-I, MHC-II, and CD80/86; (iii) decreased production of type-I interferons; (iv) delayed production of anti-inflammatory cytokines and chemokines in the lungs; and (v) impairment frequencies of functional HSV-specific CD107+IFN-γ+CD8+ T cells associated with the increased incidence of viral infection and disease. These findings suggest that age-related impairments in innate and adaptive immune responses may exacerbate respiratory viral infections and disease in the elderly.
免疫功能会随着年龄增长而下降，导致老年人更容易受到病毒感染病原体的侵害。衰老对先天性和适应性免疫系统产生负面影响，进而导致对呼吸道病毒病原体易感性增强的机制，目前仍未完全明确。在本研究中，我们使用了1型单纯疱疹病毒（HSV-1）感染的小鼠模型，该病毒可感染肺部并导致肺炎，这在老年人中虽罕见但却是严重的健康问题。在用HSV-1（KOS毒株）对年轻（6周龄）、成年（36周龄）和老年小鼠（68周龄）进行鼻内接种后，我们：（i）比较了年轻、成年和老年小鼠对感染的局部和全身免疫反应，以及（ii）将免疫反应的水平和类型与针对HSV-1感染和疾病的保护作用进行关联。与年轻和成年小鼠相比，老年小鼠表现出：（i）上皮细胞激活增加，Toll样受体3（TLR3）表达降低；（ii）树突状细胞激活增加，主要组织相容性复合体I类（MHC-I）、MHC-II类和CD80/86表达增加；（iii）I型干扰素产生减少；（iv）肺部抗炎细胞因子和趋化因子产生延迟；以及（v）功能性HSV特异性CD107⁺IFN-γ⁺CD8⁺T细胞频率受损，这与病毒感染和疾病发生率增加相关。这些发现表明，先天性和适应性免疫反应中与年龄相关的损伤可能会加剧老年人的呼吸道病毒感染和疾病。
