Multi-Step Pathogenesis and Induction of Local Immune Response by Systemic Candida Albicans Infection in an Intravenous Challenge Mouse Model
Multi-Step Pathogenesis and Induction of Local Immune Response by Systemic Candida Albicans Infection in an Intravenous Challenge Mouse Model
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DOI：
10.3390/ijms150814848
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发表时间：
2014-08-01
影响因子：
5.6
通讯作者：
Chong, Pei Pei
中科院分区：
文献类型：
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作者：
Chin, Voon-Kin;Foong, Kuan-Jeang;Chong, Pei Pei
不同的鼠种对白色念珠菌全身性感染的易感性不同，从而产生不同的宿主免疫反应，这与所使用的不同酵母菌株的毒力变化有关。因此，本研究旨在通过检测不同的参数，包括红细胞计数和相关成分，以及细胞因子和趋化因子的器官特异性表达谱，阐明临床白色念珠菌分离物（HVS6360）在小鼠静脉内攻击模型中的发病机制。与其他器官相比，受感染小鼠的肾脏和大脑有更高的真菌恢复率，肾脏和脑组织中有广泛的酵母菌浸润和中度至重度炎症。红细胞（rbc）和血红蛋白（Hb）计数在整个感染期间减少。感染72 h后，不同器官（肾、脾和脑）的模式识别受体（PRRs）、趋化因子和细胞因子转录谱发生变化。大多数PRRs、细胞因子和趋化因子的转录在感染后72 h在脾脏中被抑制，而在脑和肾中可以看到PRRs、细胞因子和趋化因子基因的持续表达。红细胞和血红蛋白计数的减少可能与白色念珠菌细胞外溶血酶和血红素加氧酶的作用有关，并与真菌生长的铁清除有关。负责产生促红细胞生成素的肾细胞可能因感染而受损，因此溶血加上促红细胞生成素诱导的红细胞补充不足的综合作用导致红细胞数量的严重减少。在全身白色念珠菌感染过程中，靶器官中不同的局部宿主免疫谱可能对未来通过免疫调节方法设计靶向免疫治疗具有重要意义。
Different murine species differ in their susceptibility to systemic infection with Candida albicans, giving rise to varied host immune responses, and this is compounded by variations in virulence of the different yeast strains used. Hence, this study was aimed at elucidating the pathogenesis of a clinical C. albicans isolate (HVS6360) in a murine intravenous challenge model by examining the different parameters which included the counts of red blood cells and associated components as well as the organ-specific expression profiles of cytokines and chemokines. Kidneys and brains of infected mice have higher fungal recovery rates as compared to other organs and there were extensive yeast infiltration with moderate to severe inflammation seen in kidney and brain tissues. Red blood cells (RBCs) and haemoglobin (Hb) counts were reduced throughout the infection period. Pattern recognition receptors (PRRs), chemokines and cytokine transcription profiles were varied among the different organs (kidney, spleen and brain) over 72 h post infections. Transcription of most of the PRRs, cytokines and chemokines were suppressed at 72 h post infection in spleen while continuous expression of PRRs, cytokines and chemokines genes were seen in brain and kidney. Reduction in red blood cells and haemoglobin counts might be associated with the action of extracellular haemolysin enzyme and haeme oxygenase of C. albicans in conjunction with iron scavenging for the fungal growth. Renal cells responsible for erythropoietin production may be injured by the infection and hence the combined effect of haemolysis plus lack of erythropoietin-induced RBC replenishment leads to aggravated reduction in RBC numbers. The varied local host immune profiles among target organs during systemic C. albicans infection could be of importance for future work in designing targeted immunotherapy through immunomodulatory approaches.