Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT; and.
Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT.
J Immunol. 2022 Mar 1;208(5):1180-1188. doi: 10.4049/jimmunol.2100915. Epub 2022 Feb 11.
Pulmonary infections elicit a combination of tissue-resident and circulating T cell responses. Understanding the contribution of these anatomically distinct cellular pools in protective immune responses is critical for vaccine development. is a highly virulent bacterium capable of causing lethal systemic disease following pulmonary infection for which there is no currently licensed vaccine. Although T cells are required for survival of infection, the relative contribution of tissue-resident and circulating T cells is not completely understood, hampering design of effective, long-lasting vaccines directed against this bacterium. We have previously shown that resident T cells were not sufficient to protect against , suggesting circulating cells may serve a critical role in host defense. To elucidate the role of circulating T cells, we used a model of vaccination and challenge of parabiotic mice. Intranasally infected naive mice conjoined to immune animals had increased numbers of circulating memory T cells and similar splenic bacterial burdens as vaccinated-vaccinated pairs. However, bacterial loads in the lungs of naive parabionts were significantly greater than those observed in vaccinated-vaccinated pairs, but despite early control of replication, all naive-vaccinated pairs succumbed to infection. Together, these data define the specific roles of circulating and resident T cells in defense against infection that is initiated in the pulmonary compartment but ultimately causes disseminated disease. These data also provide evidence for employing vaccination strategies that elicit both pools of T cells for immunity against and may be a common theme for other disseminating bacterial infections.
肺部感染会引发组织驻留 T 细胞和循环 T 细胞反应的组合。了解这些解剖上不同的细胞群体在保护性免疫反应中的贡献对于疫苗开发至关重要。 是一种高毒力的细菌，能够在肺部感染后引起致命的全身疾病，目前尚无许可的疫苗。尽管 T 细胞是 感染存活所必需的，但组织驻留 T 细胞和循环 T 细胞的相对贡献尚不完全清楚，这阻碍了针对这种细菌的有效、持久疫苗的设计。我们之前曾表明，驻留 T 细胞不足以保护免受 感染，这表明循环细胞可能在宿主防御中发挥关键作用。为了阐明循环 T 细胞的作用，我们使用了共生小鼠的接种和挑战模型。与免疫动物共生的经鼻感染的幼稚小鼠具有更多的循环记忆 T 细胞，并且与接种-接种对的脾脏细菌负荷相似。然而，幼稚共生体肺部的细菌负荷明显高于接种-接种对的观察结果，但尽管早期控制了 复制，所有幼稚-接种对都死于感染。这些数据共同定义了循环和驻留 T 细胞在防御肺部起始但最终导致播散性疾病的感染中的具体作用。这些数据还为激发针对 和可能是其他播散性细菌感染的共同主题的这两种 T 细胞群体的免疫接种策略提供了证据。
