Interleukin-33 improves local immunity during Gram-negative pneumonia by a combined effect on neutrophils and inflammatory monocytes.
Interleukin-33 improves local immunity during Gram-negative pneumonia by a combined effect on neutrophils and inflammatory monocytes.
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DOI：
10.1002/path.5601
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
van der Poll T
中科院分区：
文献类型：
--
作者：
Ramirez-Moral I;Blok DC;Bernink JH;Garcia-Laorden MI;Florquin S;Boon L;Van't Veer C;Mack M;Saluzzo S;Knapp S;Spits H;de Vos AF;van der Poll T
肺炎是一个主要的卫生保健负担，革兰氏阴性菌带来了越来越大的治疗挑战，至少在一定程度上是因为出现了多药耐药菌株。IL-33是一种多功能细胞因子，属于IL-1家族，可影响多种不同类型的细胞。在此，我们试图确定重组IL-33在常见革兰氏阴性肺炎克雷伯菌肺炎期间对宿主反应的影响。IL-33可延长致死性呼吸道感染患者1 以上的存活时间，降低原发感染部位和远处器官的细菌载量。推迟使用IL-33(3h)治疗也减少了细菌的生长和传播。IL-33在IL-33受体成分IL-1受体样1缺失的小鼠体内未观察到IL-33的保护作用。IL-33诱导了一种活跃的2型反应，其特征是2型固有淋巴样细胞聚集到肺内，并促进IL-5和IL-13的释放。然而，天然淋巴样细胞或IL-13的缺失或IL-5的阻断都不影响感染克雷伯菌的小鼠的IL-33效应。同样，在缺乏B、T和自然杀伤T细胞的小鼠中，IL-33仍然有效地减少细菌负荷。抗体介导的细胞耗竭实验表明，中性粒细胞和炎性单核细胞在抗菌防御中起着重要作用。IL-33限制肺部细菌生长的能力在中性粒细胞和炎性单核细胞都耗尽的小鼠中显著降低，但在选择性地耗尽这两种细胞中的任何一种的小鼠中没有。这些结果表明，IL-33通过对中性粒细胞和炎性单核细胞的联合作用来增强细菌性肺炎期间的宿主防御。©2020作者。《病理学杂志》由John Wiley&Sons，Ltd.代表大不列颠和爱尔兰病理学会出版。
Pneumonia represents a major health care burden and Gram‐negative bacteria provide an increasing therapeutic challenge at least in part through the emergence of multidrug‐resistant strains. IL‐33 is a multifunctional cytokine belonging to the IL‐1 family that can affect many different cell types. We sought here to determine the effect of recombinant IL‐33 on the host response during murine pneumonia caused by the common Gram‐negative pathogen Klebsiella pneumoniae. IL‐33 pretreatment prolonged survival for more than 1 day during lethal airway infection and decreased bacterial loads at the primary site of infection and distant organs. Postponed treatment with IL‐33 (3 h) also reduced bacterial growth and dissemination. IL‐33‐mediated protection was not observed in mice deficient for the IL‐33 receptor component IL‐1 receptor‐like 1. IL‐33 induced a brisk type 2 response, characterized by recruitment of type 2 innate lymphoid cells to the lungs and enhanced release of IL‐5 and IL‐13. However, neither absence of innate lymphoid cells or IL‐13, nor blocking of IL‐5 impacted on IL‐33 effects in mice infected with Klebsiella. Likewise, IL‐33 remained effective in reducing bacterial loads in mice lacking B, T, and natural killer T cells. Experiments using antibody‐mediated cell depletion indicated that neutrophils and inflammatory monocytes were of importance for antibacterial defense. The capacity of IL‐33 to restrict bacterial growth in the lungs was strongly reduced in mice depleted of both neutrophils and inflammatory monocytes, but not in mice selectively depleted of either one of these cell types. These results suggest that IL‐33 boosts host defense during bacterial pneumonia by a combined effect on neutrophils and inflammatory monocytes. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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