Alves Eric, Oakes Jared M, Simmons Joshua D, Currenti Jennifer, Coudert Jerome D, Foley Bree, Eason Joan, Halasa Natasha B, Talbot H Keipp, Castilho Jessica L, Mallal Simon A, Gaudieri Silvana, Kalams Spyros A
School of Human Sciences, University of Western Australia, Crawley, Western Australia, Australia.
Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, USA.
bioRxiv. 2025 May 28:2025.05.24.655902. doi: 10.1101/2025.05.24.655902.
Influenza remains a global health threat, infecting approximately one billion people annually and causing significant mortality, particularly among older adults. While hemagglutination inhibition (HAI) antibody titers are a standard correlate of immunity against influenza, they do not reliably predict protection in high-risk populations. Using multiomic single-cell profiling, we identified a distinct subset of adaptive-like NK cells that respond to influenza antigen, predominantly in younger females. These NK cells exhibit features of adaptive NK cells but lack classical cytomegalovirus-driven markers observed in previous studies. Notably, their increased frequency correlates with high pre-existing HAI titers, suggesting a link between adaptive-like NK responses and humoral immunity. Together, our findings identify an NK subset influenced by age and sex that may contribute to influenza protection, expanding the known diversity of adaptive-like NK cells. These insights could inform future vaccine strategies, particularly for aging populations, by integrating NK responses into assessments of vaccine efficacy.
流感仍然是全球健康威胁，每年感染约10亿人并导致大量死亡，尤其是在老年人中。虽然血凝抑制（HAI）抗体滴度是抗流感免疫力的标准关联指标，但它们不能可靠地预测高危人群的保护情况。通过多组学单细胞分析，我们鉴定出了一类独特的适应性样自然杀伤（NK）细胞亚群，它们对流感抗原产生反应，主要存在于年轻女性中。这些NK细胞表现出适应性NK细胞的特征，但缺乏先前研究中观察到的经典巨细胞病毒驱动的标志物。值得注意的是，它们频率的增加与预先存在的高HAI滴度相关，这表明适应性样NK反应与体液免疫之间存在联系。总之，我们的研究结果确定了一个受年龄和性别影响的NK亚群，它可能有助于流感保护，扩大了已知的适应性样NK细胞的多样性。这些见解可以通过将NK反应纳入疫苗疗效评估，为未来的疫苗策略提供信息，特别是针对老年人群体。
