Early or Late Bacterial Lung Infection Increases Mortality After Traumatic Brain Injury in Male Mice and Chronically Impairs Monocyte Innate Immune Function.
Early or Late Bacterial Lung Infection Increases Mortality After Traumatic Brain Injury in Male Mice and Chronically Impairs Monocyte Innate Immune Function.
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DOI：
10.1097/ccm.0000000000004273
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发表时间：
2020-05
影响因子：
8.8
通讯作者：
Loane DJ
中科院分区：
文献类型：
--
作者：
Doran SJ;Henry RJ;Shirey KA;Barrett JP;Ritzel RM;Lai W;Blanco JC;Faden AI;Vogel SN;Loane DJ
创伤性脑损伤急性期后的呼吸道感染阻碍了最佳恢复，并显著增加了总体发病率和死亡率。这项研究使用受控的皮质撞击模型，随后在小鼠中进行二次肺炎链球菌感染，研究了受损大脑和肺部之间的双向先天免疫反应。实验研究。研究实验室。成年雄性C57 BL/6 J小鼠。C57 BL/6 J小鼠进行假手术或中等水平的控制皮质撞击，并鼻内感染S.在损伤后3天或60天，使用肺炎杆菌（1，500菌落形成单位）或媒介物（磷酸盐缓冲盐水）。伤后3天，S.肺炎链球菌感染的创伤性脑损伤小鼠（TBI + Sp）的死亡率为25%，而S.肺炎感染的假手术（Sham + Sp）动物。在损伤后60天感染的TBI + Sp小鼠具有60%的死亡率，而在Sham + Sp小鼠中具有5%的死亡率。在两项研究中，与TBI + PBS小鼠相比，TBI + Sp小鼠的运动功能恢复较差。在早期和晚期感染后，与TBI + PBS小鼠相比，TBI + Sp的皮质中促炎标志物的表达增加，表明创伤后神经炎症增强。此外，TBI + Sp小鼠肺中的单核细胞在创伤性脑损伤后急性免疫抑制，不能产生白细胞介素-1 β、肿瘤坏死因子-α或活性氧。相反，与Sham + Sp小鼠相比，TBI + Sp小鼠的延迟感染后单核细胞具有更高水平的白细胞介素-1 β、肿瘤坏死因子-α和活性氧。在TBI + Sp小鼠的肺中也发现了增加的细菌负荷和病理学。创伤性脑损伤导致单核细胞功能障碍，这可能影响宿主对呼吸道感染的易感性。慢性损伤小鼠在S.肺炎感染，这表明即使在创伤性脑损伤后晚期的呼吸道感染也可能构成比目前认识到的更严重的威胁。
Respiratory infections in the postacute phase of traumatic brain injury impede optimal recovery and contribute substantially to overall morbidity and mortality. This study investigated bidirectional innate immune responses between the injured brain and lung, using a controlled cortical impact model followed by secondary Streptococcus pneumoniae infection in mice. Experimental study. Research laboratory. Adult male C57BL/6J mice. C57BL/6J mice were subjected to sham surgery or moderate-level controlled cortical impact and infected intranasally with S. pneumoniae (1,500 colony-forming units) or vehicle (phosphate-buffered saline) at 3 or 60 days post-injury. At 3 days post-injury, S. pneumoniae-infected traumatic brain injury mice (TBI + Sp) had a 25% mortality rate, in contrast to no mortality in S. pneumoniae-infected sham (Sham + Sp) animals. TBI + Sp mice infected 60 days post-injury had a 60% mortality compared with 5% mortality in Sham + Sp mice. In both studies, TBI + Sp mice had poorer motor function recovery compared with TBI + PBS mice. There was increased expression of pro-inflammatory markers in cortex of TBI + Sp compared with TBI + PBS mice after both early and late infection, indicating enhanced post-traumatic neuroinflammation. In addition, monocytes from lungs of TBI + Sp mice were immunosuppressed acutely after traumatic brain injury and could not produce interleukin-1β, tumor necrosis factor-α, or reactive oxygen species. In contrast, after delayed infection monocytes from TBI + Sp mice had higher levels of interleukin-1β, tumor necrosis factor-α, and reactive oxygen species when compared with Sham + Sp mice. Increased bacterial burden and pathology was also found in lungs of TBI + Sp mice. Traumatic brain injury causes monocyte functional impairments that may affect the host’s susceptibility to respiratory infections. Chronically injured mice had greater mortality following S. pneumoniae infection, which suggests that respiratory infections even late after traumatic brain injury may pose a more serious threat than is currently appreciated.