Mast cells inhibit intramacrophage Francisella tularensis replication via contact and secreted products including IL-4
Mast cells inhibit intramacrophage Francisella tularensis replication via contact and secreted products including IL-4
复制标题
DOI：
10.1073/pnas.0707636105
复制
发表时间：
2008-07-08
影响因子：
11.1
通讯作者：
Arulanandam, Bernard P.
中科院分区：
文献类型：
--
作者：
Ketavarapu, Jyothi M.;Rodriguez, Annette R.;Arulanandam, Bernard P.
图拉氏方济氏菌是一种胞内革兰氏阴性细菌，是肺图拉热症的病原体。图拉氏丝虫病的发病机制和先天抗性机制尚不完全清楚。肥大细胞位于粘膜组织内，是与外部环境的主要接口，在感染部位启动先天反应。经鼻注射土拉氏原虫活疫苗株(LVS)后48h，颈淋巴结和肺中的肥大细胞数量逐渐增加。我们建立了原代骨髓来源的肥大细胞-巨噬细胞共培养体系，发现肥大细胞显著抑制巨噬细胞对图拉氏杆菌LVS的摄取和生长。重要的是，与相应的野生型动物相比，肥大细胞或IL-4受体缺陷的小鼠对感染的敏感性更高。接触依赖事件和包括肥大细胞分泌的IL-4在内的分泌产物，以及来自其他细胞来源的IL-4的产生，似乎介导了观察到的保护作用。这些结果显示了肥大细胞和IL-4以前未知的作用，并为我们理解参与控制巨噬细胞内Francisella复制的先天免疫机制提供了一个新的维度。
Francisella tularensis is an intracellular, Gram-negative bacterium that is the causative agent of pulmonary tularemia. The pathogenesis and mechanisms related to innate resistance against F. tularensis are not completely understood. Mast cells are strategically positioned within mucosal tissues, the major interface with the external environment, to initiate innate responses at the site of infection. Mast cell numbers in the cervical lymph nodes and the lungs progressively increased as early as 48 h after intranasal F. tularensis live vaccine strain (LVS) challenge. We established a primary bone marrow-derived mast cell-macrophage coculture system and found that mast cells significantly inhibit F. tularensis LVS uptake and growth within macrophages. Importantly, mice deficient in either mast cells or IL-4 receptor displayed greater susceptibility to the infection when compared with corresponding wild-type animals. Contact-dependent events and secreted products including IL-4 from mast cells, and IL-4 production from other cellular sources, appear to mediate the observed protective effects. These results demonstrate a previously unrecognized role for mast cells and IL-4 and provide a new dimension to our understanding of the innate immune mechanisms involved in controlling intramacrophage Francisella replication.