Inflammatory Signatures of Pathogenic and Non-Pathogenic Leptospira Infection in Susceptible C3H-HeJ Mice.
Inflammatory Signatures of Pathogenic and Non-Pathogenic Leptospira Infection in Susceptible C3H-HeJ Mice.
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DOI：
10.3389/fcimb.2021.677999
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发表时间：
2021
影响因子：
5.7
通讯作者：
Gomes-Solecki M
中科院分区：
文献类型：
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作者：
Shetty A;Kundu S;Gomes-Solecki M
由于大多数低收入国家监测系统不足，钩端螺旋体病对全球的确切影响尚不清楚。在这项研究中，我们分析了感染后24小时和72小时涉及致病性和非致病性钩端螺旋体识别的小鼠炎症信号的差异。C3HHEJ小鼠注射非致病双曲杆菌后，血液中少量趋化因子的循环增加(5/21，24%)，而血液中不分泌细胞因子，从而导致驻留巨噬细胞、树突状细胞、中性粒细胞和NK细胞的结合而不与T细胞结合。相反，致病性问号钩端螺旋体能诱导血液中更多的趋化因子(18/21，86%)和促炎和抗炎细胞因子(11/19，58%)循环，从而导致信号级联导致巨噬细胞、树突状细胞、单核细胞、NK细胞和T细胞相互作用，而不与中性粒细胞接触。虽然中性粒细胞似乎不参与，但在感染问号钩端螺旋体后72小时，相当数量的趋化因子招募其他粒细胞，如嗜酸性粒细胞和嗜碱性粒细胞。总体而言，数据表明，预防双弯杆菌的传播与早期参与先天免疫反应有关，其特征是上调少数趋化因子，导致有效的吞噬反应，而不会导致促炎细胞因子的压倒性增加。然而，当巨噬细胞不能清除致病血清群(如问号钩端螺旋体)时，适应性反应(T细胞)被用来帮助解决问题，但由此产生的化学细胞因子风暴介导了对致病性钩端螺旋体的强大但非分解的炎症反应，导致传播、肾脏定植、病理和疾病。
The exact global impact of leptospirosis is unknown due to inadequate surveillance systems in place in most low-income countries. In this study, we analyzed the differences in mouse inflammatory signatures involved in pathogenic versus non-pathogenic Leptospira recognition at 24h and 72h post infection. Injection of C3H-HeJ mice with non-pathogenic L. biflexa increased circulation of a few chemokines (5/21, 24%) without secretion of cytokines in blood that resulted in engagement of resident macrophages, dendritic cells, neutrophils and NK cells without engagement of T cells. In contrast, pathogenic L. interrogans induced circulation of a much higher panel of chemokines (18/21, 86%) and pro- and anti-inflammatory cytokines (11/19, 58%) in blood with a resulting signaling cascade leading to engagement of macrophages, dendritic cells, monocytes, NK cells and T cells without engagement of neutrophils. Although neutrophils do not appear to be engaged, a considerable number of chemokines that recruit other granulocytes such as eosinophils and basophils were also increased at 72h post infection with L. interrogans. Overall, the data suggest that prevention of dissemination of L. biflexa is associated with an early engagement of the innate immune response characterized by upregulation of a few chemokines that results in an efficacious phagocytic response without an overwhelming increase of pro-inflammatory cytokines. However, when macrophages fail to clear a pathogenic serovar such as L. interrogans, the adaptive response (T cells) is engaged to help out, but the resulting chemo-cytokine storm mediates a robust but non-resolving inflammatory response to pathogenic Leptospira that results in dissemination, kidney colonization, pathology and disease.