Pathogenesis of Borrelia burgdorferi and Babesia microti in TLR4-Competent and TLR4-dysfunctional C3H mice.
Pathogenesis of Borrelia burgdorferi and Babesia microti in TLR4-Competent and TLR4-dysfunctional C3H mice.
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伯氏疏螺旋体和微小巴贝斯虫在tlr4正常和tlr4功能障碍C3H小鼠中的发病机制
DOI：
10.1111/cmi.13350
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发表时间：
2021-09
影响因子：
3.4
通讯作者：
Parveen N
中科院分区：
文献类型：
--
作者：
Akoolo L;Djokic V;Rocha SC;Parveen N
Toll样受体（TLRs）是一类宿主细胞的跨膜蛋白。TLR2和TLR4显示在巨噬细胞、中性粒细胞和树突状细胞表面，并识别结构上保守的微生物特征，称为病原体相关分子模式（Pathogen associated molecular patterns, PAMPs）。C3H小鼠对蜱传病原体敏感；莱姆病引起的伯氏疏螺旋体，表现为关节炎和心脏炎；顶复原虫，微小巴贝斯虫（Bm），引起与红细胞减少症和血红蛋白尿相关的严重寄生虫病。伯氏疏螺旋体缺乏典型的TLR4配体脂多糖（LPS）， TLR配体的种类尚不清楚。只有通过TLR2信号的伯氏疏螺旋体脂蛋白被确定为这些病原体对TLR2/TLR4的PAMPs。C3H小鼠分别感染每种病原体后，脾脏B、T和FcR+细胞的比例均增加，而它们的共感染显著降低了这些细胞的水平，并增加了特定器官的伯氏螺旋体负荷。在共感染的C3H/HeJ小鼠中观察到最明显的炎性关节炎。两种小鼠的寄生水平和Bm的溶解动力学无显著差异。转染的HEK293细胞表现出明显的伯氏疏螺旋体通过TLR2和一定程度上通过TLR4的信号传导，而Bm和感染的红细胞没有表现出任何反应，证实了我们在小鼠中的结果。伯氏疏螺旋体在感染早期通过未知配体（用问号表示）刺激C3H/HeN小鼠的TLR4可抑制TLR2的表达。在缺乏功能性TLR4的情况下，C3H/HeJ小鼠中TLR2表达的增加可能会增强定定的伯氏疏螺旋体三酰基化脂蛋白的信号传导，导致炎症性莱姆病关节炎的增加，特别是在伯氏疏螺旋体感染和C3H/HeJ小鼠共感染期间，这与更高的淋巴细胞浸润和滑膜增生有关。莱姆病螺旋体的体外TLR2信号传导，以及表达的Bm或irbc（用十字标记）缺乏通过TLR2/TLR4的信号传导支持该模型。
Toll‐like receptors (TLRs) are a class of membrane‐spanning proteins of host cells. TLR2 and TLR4 are displayed on the surface of macrophages, neutrophils and dendritic cells and recognise structurally conserved microbial signatures defined as Pathogen associated molecular patterns (PAMPs). C3H mice are susceptible to tick‐borne pathogens; Lyme disease causing Borrelia burgdorferi that manifests arthritis and carditis and Apicomplexan protozoan, Babesia microti (Bm) that causes significant parasitemia associated with erythrocytopenia and haemoglobinuria. B. burgdorferi lacks typical TLR4 ligand lipopolysaccharides (LPS) and Bm TLR ligand(s) remain unknown. Only Borrelia lipoproteins that signal through TLR2 are established as PAMPs of these pathogens for TLR2/TLR4. Infection of C3H mice with each pathogen individually resulted in increase in the percentage of splenic B, T and FcR+ cells while their co‐infection significantly diminished levels of these cells and caused increased B. burgdorferi burden in the specific organs. The most pronounced inflammatory arthritis was observed in co‐infected C3H/HeJ mice. Parasitemia levels and kinetics of resolution of Bm in both mice strains were not significantly different. Transfected HEK293 cells showed pronounced signalling by B. burgdorferi through TLR2 and to some extent by TLR4 while Bm and infected erythrocytes did not show any response confirming our results in mice. TLR4 stimulation in C3H/HeN mice by B. burgdorferi by unknown (indicated by a question mark) ligand(s) early in infection causes suppression of TLR2 expression. An increase in TLR2 expression in C3H/HeJ mice in the absence of a functional TLR4 possibly enhances signaling by Tri‐Acylated lipoproteins of colonized B. burgdorferi resulting in an increase in inflammatory Lyme arthritis, particularly during co‐infection that is associated with higher lymphocytes infiltration and hyperplasia of synovium in B. burgdorferi infected, and co‐infected C3H/HeJ mice. In vitro TLR2 signaling by Lyme spirochetes, and the lack of signaling through TLR2/TLR4 by egressed Bm or iRBCs (marked by a cross) support this model.
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影响因子：
4.2
作者：
Chan K;Marras SA;Parveen N
通讯作者：
Parveen N
DOI：
10.1073/pnas.1013776108
发表时间：
2011-03-01
影响因子：
11.1
作者：
Cervantes, Jorge L.;Dunham-Ems, Star M.;Salazar, Juan C.
通讯作者：
Salazar, Juan C.
影响因子：
3.9
作者：
Debierre-Grockiego, Francoise;Smith, Terry K.;Cornillot, Emmanuel
通讯作者：
Cornillot, Emmanuel
影响因子：
2.6
作者：
Brown, Wendy C.;Norimine, Junzo;Goff, Will L.
通讯作者：
Goff, Will L.
影响因子：
11.8
作者：
Diuk-Wasser MA;Liu Y;Steeves TK;Folsom-O'Keefe C;Dardick KR;Lepore T;Bent SJ;Usmani-Brown S;Telford SR 3rd;Fish D;Krause PJ
通讯作者：
Krause PJ