B cell deficiency induces cytotoxic memory CD8+ T cells during influenza-associated bacterial pneumonia.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Leigh M Miller, Alexis M Duray, Ellyse M Cipolla, Flavia Rago, Brooke P Dresden, Kristen L Parenteau, Abhigya Gupta, John F Alcorn
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Abstract

Influenza-associated bacterial super-infections in the lung lead to increased morbidity and mortality. Nearly all people have pre-existing memory to influenza virus, which can protect against subsequent infection in the lung. This study explored the role B cells play in protection against bacterial (Staphylococcus aureus or Klebsiella pneumoniae) super-infection with previous heterotypic influenza memory. B cell deficiency resulted in an increased inflammatory lung environment and lung tissue injury during super-infection. Loss of B cells increased populations of memory CD8+ T cells in the lung and these CD8+ T cells were transcriptionally and functionally distinct from WT mice. Use of antibody-deficient mouse models showed that this phenotype was specifically due to loss of antibody production from B cells. Passive immunization with influenza-antibody serum in B cell deficient mice rescued the CD8+ T cell phenotype. CD8+ T cell depletion and lethal super-infection challenge experiments showed that the cytotoxic memory CD8+ T cells from B cell deficient mice protect against super-infection bacterial burden and mortality. These findings provide insight into the importance of B cells for regulating immune responses against infection.

B细胞缺乏在流感相关性细菌性肺炎期间诱导细胞毒性记忆CD8+ T细胞。
与流感相关的肺部细菌超级感染导致发病率和死亡率增加。几乎所有人都对流感病毒有预先的记忆,这可以防止随后的肺部感染。本研究探讨了B细胞在抵抗细菌(金黄色葡萄球菌或肺炎克雷伯菌)超感染与既往异型流感记忆中的作用。B细胞缺乏导致炎症性肺环境增加和肺组织损伤。B细胞的缺失增加了肺中记忆性CD8+ T细胞的数量,这些CD8+ T细胞在转录和功能上与WT小鼠不同。抗体缺陷小鼠模型的使用表明,这种表型是由于B细胞抗体产生的损失。B细胞缺陷小鼠的流感抗体血清被动免疫可挽救CD8+ T细胞表型。CD8+ T细胞耗竭和致死性超感染攻击实验表明,来自B细胞缺陷小鼠的细胞毒性记忆CD8+ T细胞可防止超感染细菌负担和死亡。这些发现提供了对B细胞在调节抗感染免疫反应中的重要性的见解。
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来源期刊
Journal of Clinical Investigation
Journal of Clinical Investigation 医学-医学:研究与实验
CiteScore
24.50
自引率
1.30%
发文量
1034
审稿时长
2 months
期刊介绍: The Journal of Clinical Investigation, established in 1924 by the ASCI, is a prestigious publication that focuses on breakthroughs in basic and clinical biomedical science, with the goal of advancing the field of medicine. With an impressive Impact Factor of 15.9 in 2022, it is recognized as one of the leading journals in the "Medicine, Research & Experimental" category of the Web of Science. The journal attracts a diverse readership from various medical disciplines and sectors. It publishes a wide range of research articles encompassing all biomedical specialties, including Autoimmunity, Gastroenterology, Immunology, Metabolism, Nephrology, Neuroscience, Oncology, Pulmonology, Vascular Biology, and many others. The Editorial Board consists of esteemed academic editors who possess extensive expertise in their respective fields. They are actively involved in research, ensuring the journal's high standards of publication and scientific rigor.
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