抗白念珠菌感染的疫苗及抗体研究进展

白念珠菌是与人类共生的条件致病真菌,能引起免疫力低下患者皮肤黏膜和全身系统性持续感染.系统性念珠菌病是引起免疫力低下患者死亡的主要原因之一.由于临床缺乏念珠菌病的早期诊疗手段、可用的抗真菌药物种类有限且毒副作用大、耐药菌株越来越普遍、新药研发难度大等因素,抗真菌治疗依然面临着严峻挑战.目前有较多研究者致力于阐明白念珠菌感染的宿主免疫应答机制,并试图研发抗白念珠菌感染的免疫治疗方法,使免疫治疗有望成为预防和治疗真菌感染的有效手段.该文将几种抗白念珠菌感染的疫苗和抗体研究进展作简要概述,旨在为新型抗白念珠菌感染疫苗及抗体的研究提供参考.     

体液免疫抗白念珠菌感染的研究

探讨抗白念珠菌IgY及其免疫血清对多种动物模型感染白念珠菌的保护作用。制备烧伤继发感染白念珠菌大鼠、白念珠菌性阴道炎小鼠及免疫功能低下小鼠多种动物感染模型 ,分别应用抗白念珠菌IgY、鼠免疫血清和生理盐水对照 ,观察比较各自的作用。抗白念珠菌IgY对烧伤继发感染白念珠菌大鼠及白念珠菌性阴道炎小鼠均有明显的保护作用 ;鼠免疫血清则对阻止远程靶器官的白念珠菌扩散有较好的作用。体液免疫成份抗白念珠菌IgY及其免疫血清对烧伤继发感染白念珠菌大鼠、白念珠菌性阴道炎小鼠及免疫功能低下小鼠均有良好的保护作用。     

抗白念珠菌感染的协同作用机制研究进展

<正>白念珠菌 (Candida albicans,C. albicans)是一种条件致病菌,当人体免疫系统受损或体内正常微生物菌群失衡时,该菌可引起浅部感染,甚至会通过血液传播到器官组织引起侵袭性白念珠菌感染,严重危害人类的生命健康。近年来,随着免疫缺陷类疾病患病率的上升,化疗药物、糖皮质激素、免疫抑制剂等的广泛应用,白念珠菌感染逐渐增多^[1]。     

山苍子油对小鼠系统性白念珠菌感染的影响

目的研究山苍子油对小鼠系统性白念珠菌感染的治疗作用。方法建立小鼠系统性白念珠菌感染模型,观察给药后小鼠中位生存时间,并检测给药后小鼠肾脏菌落形成单位计数。结果山苍子油能明显延长小鼠的中位生存时间,降低肾脏菌落形成单位计数。结论山苍子油对小鼠系统性白念珠菌感染具有治疗作用,值得进一步研究和开发。     

中草药抗白念珠菌作用研究进展

白念珠菌,是人类最常见的真菌病原体,可引起各种浅表及深部真菌病,对常用抗真菌药物易产生耐药.文章就近年来有关中草药抗白念珠菌的相关临床及实验研究进行综述,主要从中草药抗白念珠菌的作用机制及其活性成分、单味及复方中草药制剂抗白念珠菌作用、中西药协同抗白念珠菌作用几个方面进行阐述.     

中药抗白念珠菌研究新进展

以白念珠菌为主的真菌感染近年来呈上升态势,氟康唑等一线抗真菌药物因长期应用导致耐药菌株不断出现,中药在抗真菌感染方面具有独特的优势。本课题组在多项国家与省级课题资助下,对中药的体内外抗真菌作用及机制进行了较系统深入的研究,现结合课题组自身与国内外在中药抗真菌感染领域的最新研究成果,对中药抗真菌(主要是白念珠菌)近5年的研究进展进行综述。     

苦寒类中药抗白念珠菌的研究进展

深部真菌(主要为白念珠菌)感染现象在临床中越来越常见,真菌耐药已经成为目前治疗的主要难题.传统中医理论认为“苦寒燥湿”类中药能有效治疗各种感染,对寻找抗耐药白念珠菌新药及协同药物具有一定的指导意义.该文主要总结阐述苦寒类中药抗真菌研究进展.     

Th1/Th2细胞免疫应答在抗白念珠菌感染中的作用

白念珠菌是常见的条件致病性真菌,Th细胞激活的亚群类型决定了机体抗白念珠菌的特异性细胞免疫结果。当Th1细胞激活,机体对白念珠菌有抵抗力;而当Th2细胞激活,机体对白念珠菌易感。由Th1细胞分泌或能刺激Th1细胞分化的IFN－γ、IL－2、IL－12等细菌因子增强机体对白念珠菌的抵抗力;而Th2细胞分泌的IL－4、IL－10等细菌因子则相反。     

都柏林念珠菌与白念珠菌的实验室鉴别进展

都柏林念珠菌是新命名的可以产生芽管和厚壁孢子的致病念珠菌,常规的实验室检测方法很难将其与白念珠菌相鉴别。本文综述了都柏林念珠菌和白念珠菌的生物形态学特征及形态学、血清学、分子生物学鉴别进展。     

大蒜素体外抗白念珠菌生物膜作用的初步研究

目的研究大蒜素对体外白念珠菌生物膜的影响。方法 MTT法评价大蒜素对白念珠菌生物膜形成及细胞黏附的影响;血清芽管计数法评价大蒜素对白念珠菌芽管形成的影响。结果低浓度(4μg/mL)和高浓度(64μg/mL)大蒜素对白念珠菌生物膜形成的抑制率分别为(23.0±1.1)%和(95.6±0.3)%;32μg/mL大蒜素对早期(0h)、中期(12h)及成熟期(48h)生物膜的抑制率分别为(88.5±0.5)%、(63.3±0.8)%和(52.3±1.1)%;与空白对照组相比,不同浓度大蒜素(4～32μg/mL)对培养30min、60min、90min、120min的白念珠菌细胞黏附均有显著抑制作用(P0.05);空白对照组芽管形成率为(91.2±1.6)%,64μg/mL大蒜素组为(2.2±1.2)%。结论大蒜素对体外白念珠菌生物膜有较明显的抑制作用。     

Low dose of Concanavalin-A enhances innate immune response and prevents liver injury in mice infected with Candida albicans

The mechanisms through which Candida albicans is recognized by immune cells and how it triggers host defence are not completely understood. In this study, we evaluated the effect of Concanavalin-A on the clearance of C. albicans by infected mice and their production of proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Subgroups of 5 animals were pretreated with Con-A (250 mug mL(-1) PBS) and after 96 h were infected intraperitoneally with 10(7) cells of C. albicans CR15 (an isolate from a HIV+ person); 30 min, 2, 6, 24 or 72 h after infection the mice were sacrificed. Phagocytosis of C. albicans by peritoneal macrophages increased 30 min after infection in mice pretreated with Con-A. The liver presented the greatest number of CFUs, and this number was reduced by pretreatment with Con-A. Control animals infected with C. albicans presented a significant increase in plasmatic alanine aminotransferase, which was not observed in mice treated with Con-A. Two hours after infection the production of TNF-alpha in the liver of mice pretreated with Con-A was significantly increased. These results suggest that a single dose of Con-A caused a beneficial modulating action of the inflammatory response during infection with C. albicans.     

大鼠白念珠菌支气管肺感染时肺组织Toll样受体2的表达及意义

目的 探讨Toll样受体2(TLR2)在白念珠菌支气管肺感染大鼠肺组织模型中的表达及意义.方法 建立白念珠菌支气管肺感染大鼠模型,观察感染后肺组织病理形态学改变,采用免疫组织化学法观察感染后不同时间(第3天、第7天)白念珠菌支气管肺感染大鼠肺组织TLR2的表达,并与未感染组进行比较.结果 大鼠白念珠菌支气管肺感染后肺组织TLR2表达水平明显升高.结论 白念珠菌支气管肺感染肺组织TLR2表达增高可能参与感染的炎症反应.     

大鼠支气管肺白念珠菌感染后血清IL-17水平及意义

目的探讨大鼠支气管肺白念珠菌感染后血清白细胞介素17(IL-17)的变化及意义。方法将24只Sprague Dawley(以下简称SD)健康雄性鼠随机分为3组,每组8只,免疫低下+白念珠菌感染组(阳性对照组);免疫低下+生理盐水组(阴性对照组);免疫正常+白念珠菌感染组(实验组)。因为实验过程中存在大鼠死亡,最终每组各有6只大鼠完成实验。系统应用糖皮质激素建立免疫低下的大鼠模型;实验组及阳性对照组使用标准白念珠菌菌株混悬液经气管插管注入而建立感染模型;阴性对照组使用生理盐水作对照。感染后第1、3、5、7天使用尾静脉取血分离血清;酶联免疫吸附法(ELISA)检测血清IL-17水平;第7天取血后处死大鼠,取右肺下叶组织进行HE染色观察。结果第3、5天实验组血清IL-17水平高于对照组,而第1、7天3组间无差异;两对照组IL-17水平无差异。肺组织病理:实验组呈明显炎症反应;阳性对照组呈轻微炎症反应;阴性对照组未见明显炎性细胞浸润。结论大鼠白念珠菌支气管肺感染后,免疫正常的大鼠在感染中期血清IL-17水平升高,IL-17可能通过促进中性粒细胞在气道的聚集而参与炎症反应;IL-17的水平与机体炎症反应呈正相关;IL-17在气道白念珠菌感染后炎症介导及机体防御机制的调动中起一定作用。     

In vitro response to Candida albicans in cultures of whole human blood from young and aged donors

Invasive infections with opportunistic fungi, such as Candida albicans, have become an increasing problem in aged adults in recent years. This work investigates the influence of human ageing on C. albicans recognition by toll-like receptors (TLRs), essential components of the innate immune system, using a cohort of 96 young (15-42 years) and aged (>70 years) human volunteers. No significant differences between aged and young donors were observed on (1) cell surface TLR2, TLR6 and TLR4 expression on lymphocytes, monocytes and granulocytes, (2) production of cytokines [IL-8, IL-1beta, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and IL-12p70] and prostaglandin E(2) (PGE(2)) by whole human blood in response to C. albicans and (3) fungicidal activity of whole blood. A statistically significant higher titre of natural anti-C. albicans antibodies was found in plasma of volunteers between 80 and 95 years old when compared with other age groups, probably as a consequence of the increased levels of serum Ig that has been described in elderly subjects. Therefore, the results indicate that the increased susceptibility to C. albicans infections in the elderly is not a consequence of defects in TLRs expression or signalling, nor of an impaired fungicidal activity of blood.     

Innate versus adaptive immunity in Candida albicans infection

Candida albicans is a common opportunistic pathogen, causing both superficial and systemic infection. Clinical observations indicate that mucocutaneous infections are commonly associated with defective cell-mediated immune responses, whereas systemic infection is more frequently seen in patients with deficiencies in neutrophil number or function. Analysis of mechanisms of host resistance against gastrointestinal and oral infection in mouse models has demonstrated an absolute dependence on CD4(+) T cells, although clearance also involves phagocytic cells. Both IL-12 and TNF-alpha appear to be important mediators, but mouse strain-dependent variations in susceptibility to infection may be related to T-cell enhancement of production of phagocytic cells by the bone marrow. In murine systemic infection, the role of innate and adaptive responses is less well defined. Studies in immunodeficient and T-cell-depleted mice suggest that clearance of the yeast may be predominantly a function of the innate response, whereas the adaptive response may either limit tissue damage or have the potential to cause immunopathology, depending on the host genetic context in which the infection takes place.     

Immunomodulatory and protective effect of probiotic Lactobacillus casei against Candida albicans infection in malnourished mice

The effect of Lactobacillus casei CRL 431 (Lc), when administered as a supplement to a repletion diet, on the resistance of malnourished mice to Candida albicans infection was studied. Weaned mice were malnourished by being given a protein-free diet (PFD) for 21 days. The malnourished mice were then fed a balanced conventional diet (BCD) for 7 days or BCD for 7 days with supplemental Lc on days 6 and 7 (BCD+Lc). Malnourished (MNC) and well-nourished (WNC) mice were used as controls. At the end of the treatments the mice were infected intraperitoneally with C. albicans. Animals that had received probiotics had improved survival and resistance against this infection compared to those in the BCD and MNC groups. The number and fungicidal activity of phagocytes, and the concentrations of tumor necrosis factor-α, interferon-γ and interleukin-6 (IL-6), increased in blood and infected tissues in all experimental groups, but MNC mice showed lower concentrations than those in the WNC group. BCD and BCD+Lc mice showed higher concentrations of these variables than those in the MNC group, but only the BCD+Lc group presented values similar to the WNC mice. Malnutrition also impaired the production of IL-17 and IL-10 in response to infection. Both repletion treatments normalized IL-17 concentrations, but IL-10 in the BCD+Lc group was significantly higher than in WNC mice. The addition of L. casei to the repletion diet normalized the immune response against C. albicans, allowing efficient recruitment and activation of phagocytes, as well as effective release of pro-inflammatory cytokines. In addition, probiotic treatment induced an increase in IL-10 concentrations, which would have helped to prevent damage caused by the inflammatory response.     

Interspecific hybridisation between Candida albicans and Candida tropicalis

Abstract Protoplasts from auxotrophic mutants of Candida albicans and Candida tropicalis were produced by snail enzyme treatment and their fusion was induced with polyethylene glycol (PEG). During selective regeneration, nutritionally complemented interspecific hybrids were obtained. Their cells contained one nucleus, and the DNA content per cell was higher than in the parents. The isoenzymic and sugar assimilation patterns of the mutants, and those of the hybrids and the products after their haploidisation, were also analysed. The results indicated that the hybrids were partial alloploids containing the total chromosomal set of either of the parental species and one or a few chromosomes of the other.     

Azole sensitivity in Candida albicans

Abstract In the present study, we assessed the influence of three culture media on the susceptibility 'in vitro' of twenty four clinical strains belonging to Candida albicans against three imidazole-derivatives and also, we investigated the situation of azole sensitivity in three of these strains.