Department of Hematology, Medical Oncology and Pneumology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Department of Dermatology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Front Immunol. 2019 Feb 4;10:123. doi: 10.3389/fimmu.2019.00123. eCollection 2019.
ß2 integrin receptors consist of an alpha subunit (CD11a-CD11d) and CD18 as the common beta subunit, and are differentially expressed by leukocytes. ß2 integrins are required for cell-cell interaction, transendothelial migration, uptake of opsonized pathogens, and cell signaling processes. Functional loss of CD18-termed leukocyte-adhesion deficiency type 1 (LAD1)-results in an immunocompromised state characterized by frequent occurrence of severe infections. In immunosuppressed individuals is a frequent cause of invasive pulmonary fungal infection, and often occurs in patients suffering from LAD1. Here, we asked for the importance of CD11b/CD18 also termed MAC-1 which is required for phagocytosis of opsonized conidia by polymorphonuclear neutrophils (PMN) for control of pulmonary infection. We show that CD11b mice infected with were unaffected in long term survival, similar to wild type (WT) mice. However, bronchoalveolar lavage (BAL) performed 1 day after infection revealed a higher lung infiltration of PMN in case of infected CD11b mice than observed for WT mice. BAL derived from infected CD11b mice also contained a higher amount of leukocyte-attracting CCL5 chemokine, but lower amounts of proinflammatory innate cytokines. In accordance, lung tissue of infected CD11b mice was characterized by lower cellular inflammation, and a higher fungal burden. In agreement, CD11bPMN exerted lower phagocytic activity on serum-opsonized conidia than WT PMN . Our study shows that MAC-1 is required for effective clearance of by infiltrating PMN, and the establishment of an inflammatory microenvironment in infected lung. Enhanced infiltration of CD11b PMN may serve to compensate impaired PMN function.
β2 整合素受体由一个α亚基（CD11a-CD11d）和 CD18 作为共同的β亚基组成，在白细胞中差异表达。β2 整合素是细胞间相互作用、跨内皮迁移、调理病原体摄取和细胞信号转导过程所必需的。CD18 功能丧失——称为白细胞黏附缺陷 1 型（LAD1）——导致免疫功能受损，其特征是频繁发生严重感染。在免疫抑制个体中，是侵袭性肺部真菌感染的常见原因，并且经常发生在患有 LAD1 的患者中。在这里，我们询问了 CD11b/CD18（也称为 MAC-1）对吞噬调理后的分生孢子的多形核粒细胞（PMN）在控制肺部感染中的重要性。我们发现，感染 的 CD11b 小鼠在长期存活方面没有受到影响，与野生型（WT）小鼠相似。然而，感染后 1 天进行的支气管肺泡灌洗（BAL）显示，感染 CD11b 小鼠的 PMN 肺部浸润高于 WT 小鼠。来自感染 CD11b 小鼠的 BAL 还含有更高量的白细胞吸引趋化因子 CCL5，但促炎先天细胞因子的量较低。相应地，感染 CD11b 小鼠的肺组织表现出较低的细胞炎症和较高的真菌负荷。一致地，CD11bPMN 对血清调理的分生孢子的吞噬活性低于 WT PMN。我们的研究表明，MAC-1 是 PMN 有效清除的必需条件，并且在感染的肺部建立炎症微环境。CD11b PMN 的增强浸润可能有助于补偿 PMN 功能受损。
