巨噬细胞对结核分枝杆菌免疫反应的研究进展

巨噬细胞是结核分枝杆菌感染人体后的主要寄居场所。细胞介导的免疫反应是机体抗结核分枝杆菌的主要免疫保护机制,巨噬细胞通过吞噬、自噬、抗原提呈、产生多种细胞因子、自由基。以及细胞凋亡等多种途径杀灭结核分枝杆菌。笔者就巨噬细胞对结核分枝杆菌的免疫反应机制做一综述。     

肠道菌群在结核分枝杆菌感染及其治疗中的相关性研究进展

结核病是由结核分枝杆菌(Mycobacterium tuberculosis,Mtb)感染而引起的慢性传染性疾病。Mtb感染人类后,其感染状态与宿主自身的免疫、代谢、遗传学机制等密切相关。肠道菌群及其代谢物通过参与宿主免疫反应和新陈代谢在结核病的病理生理过程及其治疗中其起重要作用。本文将从“肺-肠轴”、肠道菌群代谢产物在Mtb感染中的作用、结核化疗对肠道菌群的影响及肠道菌群在结核治疗中的潜在作用进行综述。     

结核分枝杆菌感染需要治疗吗?

正结核分枝杆菌俗称结核杆菌,是引起结核病的病原菌,可侵犯全身各器官,但以肺结核最为多见。结核病至今仍为重要的传染病。1.感染结核分枝杆菌有什么表现?人体感染结核分枝杆菌后可表现为潜伏性结核分枝杆菌感染和结核病两种状况。潜伏性结核分枝杆菌感染(简称"潜伏性结核感染")定义为细菌活性持续存在,但受到免疫控制,所以没有活动性结核病临床症状的状态。     

结核分枝杆菌北京基因型与不良治疗结局的研究进展

感染结核分枝杆菌北京基因型患者与复发、治疗失败等不良结局有着密切的关联,本研究归纳北京基因型与治疗不良结局间的关联。分析北京基因型在蛋白质表达、脂质结构与免疫力方面与其他基因型相比的特别之处,以及由此而导致的毒性增强、免疫逃避与削弱宿主反应能力、推进疾病从潜伏发展为活动性结核等生化特性,并探讨引起北京基因型结核分枝杆菌传播的可能协同影响因素。     

肺结核病人细胞因子的研究进展

结核病是由结核分枝杆菌感染人体、由T淋巴细胞介导引起Ⅳ型超敏反应,是危害公共卫生健康的主要传染病之一。肺结核患者体内细胞因子变化、细胞因子基因多态性与结核易感性是肺结核免疫学研究热点。研究表明,肺结核病人在经过相关抗结核药物治疗后机体本身的细胞因子会发生变化,细胞因子基因碱基的替换会增加肺结核感染率。肺结核的发生发展及治疗效果都与人体免疫密切相关,探讨肺结核患者体内细胞因子的变化对肺结核进展及预后判断有重要意义。本文将对近年来肺结核病人细胞因子的变化进行概述。     

国外非结核分枝杆菌医院感染暴发的研究现状: 1985—2023年

非结核分枝杆菌在环境中广泛存在, 可因医疗用水、器械污染等引起血流、皮肤和软组织感染, 并导致感染暴发。本文通过在PubMed检索非结核分枝杆菌暴发事件相关的文献, 总结分析1985—2023年国外非结核分枝杆菌医院感染暴发情况, 以期为今后非结核分枝杆菌感染防控措施的制定和监管提供参考。     

与结核感染相关的转录及免疫生物标志物研究进展

结核病是严重危害人类健康的传染病, 2020年全球约四分之一人口感染结核分枝杆菌, 其中大部分是潜伏感染者。约5%～10%的潜伏感染者可进展为活动性结核病。通过生物标志物识别潜伏结核感染与活动性结核, 并寻找能可靠预测结核由潜伏感染进展为活动性结核的生物标志物, 以此筛选出具有高进展风险的潜伏结核感染人群进行预防性治疗, 是控制结核病最有效的策略之一。本文从转录组和免疫组两个方面对识别结核感染及预测潜伏感染进展为活动性结核的生物标志物研究进展进行阐述, 旨在为结核病控制提供新的思路。     

结核病易感基因研究进展

结核病研究虽然长达几个世纪之久,但到目前为止,仍然是由单一病原菌导致死亡人数最多的疾病,并且近年来呈现死灰复燃之势,为此WHO于1993年宣布结核病为新发的全球公共卫生事件.近年来,发达国家通过研制有效的抗菌药和改善社会经济条件以降低结核病发病率和死亡率,但是结核病仍为发展中国家的主要健康威胁之一.根据2009年WHO估计,2007年全球结核病新发病例为927万,其中我国约为130万[1].流行病学调查显示,不到10%的结核分枝杆菌感染者会发展成为活动性结核病,而大多数的感染者却能控制或者清除结核分枝杆菌[2].感染结核分枝杆菌能否发展成为临床症状的结核病与机体免疫状态相关,而机体的免疫状态很大程度上是由宿主基因决定的,一系列的研究已经证明宿主的遗传因素在结核病发展过程中发挥着重要的作用[3-6].     

microRNA与结核分枝杆菌感染的致病机制研究进展

结核病是一类严重危害人类生命健康的呼吸道传染病,由结核分枝杆菌感染引起,在全球内影响重大。结核病在早期诊断后可获得较好的治疗效果,同时,在结核分枝杆菌感染后,微小RNA(microRNA,miRNA)参与结核病发病机制,与其发生发展存在一定关系。因此,本文就miRNA与结核分枝杆菌感染的致病机制的研究进展进行综述,为今后结核病的早期预防、及时治疗等提供新的研究思路。     

非结核分枝杆菌肺部感染及其耐药性分析

非结核分枝杆菌(NTM)是一种环境分枝杆菌,近年来在国内外各地不断出现NTM病暴发流行,许多是由于水源消毒管理不严,或医院手术器械被污染、创口污染所引起.随着免疫抑制剂的应用,艾滋病人数的增多,NTM引起肺部感染的发病率正在增加.为研究肺部非结核分枝杆菌的感染及耐药特征,我们对近几年结核病人痰标本的非结核分枝杆菌进行分离,测定了其药物敏感性.     

Matrix metalloproteases and their association to tuberculosis

Tuberculosis (TB) remains as the single most relevant bacterial infectious disease worldwide, causing nearly eight million new cases annually, with an estimated death toll close to two million people per year. The World Health Organization estimates that one third of the world population is latently infected with Mycobacterium tuberculosis (Mtb). Latent TB reactivation remains as the most common cause of new cases of active TB, given inflammation, necrosis and pulmonary cavitation lead to tissue erosion and dissemination to uninfected hosts. Current knowledge of events regulating exacerbated inflammatory responses is scarce. However, participation of components from both the infectious agent and the host is suspected. In this regard, likely candidates to participate in cavitation are matrix metalloproteases (MMPs), a family of proteolytic enzymes required for degrading and reconstructing tissue either in normal or pathological conditions, as well as for processing signaling molecules including cytokines and chemokines. Some studies have reported induction of MMPs genes in response to mycobacterial infection in cellular models, or how inhibiting MMPs action modify the course of tuberculosis infection in murine models.     

Mucosal immunization with recombinant heparin-binding haemagglutinin adhesin suppresses extrapulmonary dissemination of Mycobacterium bovis bacillus Calmette-Guérin (BCG) in infected mice

It is generally accepted that cellular immunity plays a critical role in the protection against Mycobacterium tuberculosis, an intracellular pathogen. Recently, however, an increasing number of reports indicate the important contribution of humoral immunity against mycobacterial infection. Since M. tuberculosis establishes its primary lesion in the lung, induction of humoral immunity in the airway tract by mucosal immunization regime could provide protective immunity against tuberculosis. In this study, mycobacterial heparin-binding haemagglutinin adhesin (HBHA) was used as an immunization antigen because HBHA is an essential virulence factor required for the infection of lung epithelial cells and extrapulmonary dissemination of mycobacteria. The effects of intranasal immunization with a yeast-expressed recombinant (r) HBHA co-administered with a mucosal adjuvant cholera toxin (CT) on the induction of humoral and cellular immunity were examined, and its protective efficacy against pulmonary challenge infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG) was evaluated. HBHA-specific antibodies were induced in serum and airway tract of immunized mice, which specifically recognized native HBHA expressed on M. bovis BCG. Th1-type immunity against mycobacterial antigens was also enhanced in the lung of immunized mice after pulmonary BCG infection. Furthermore, the immunization suppressed bacterial load in the spleen after pulmonary BCG infection. These results indicate that systemic and local humoral immunity induced by the HBHA-based mucosal vaccine impairs extrapulmonary dissemination, thus providing immune protection against mycobacterial infection.     

Mycobacterial infection is an important infective complication in British Asian dialysis patients.

To define the extent and nature of mycobacterial infection in patients on an adult dialysis unit whose catchment population contains a large proportion of non-Caucasian subjects, a retrospective survey of all new patients accepted onto our maintenance dialysis programme between January 1987 and December 1989 was carried out. Twenty-six Asian, 13 Afro-Caribbean, two Oriental and 170 Caucasian patients were accepted onto the dialysis programme in the three-year recruitment period. Eight of the 26 Asian patients, but none of the others, had developed mycobacterial infection by the end of December 1990. One patient had a cerebral tuberculoma with miliary mottling on chest X-ray, one pulmonary tuberculosis, one tuberculous adenitis and 5 tuberculous peritonitis (four due to Mycobacterium tuberculosis and one Mycobacterium kansasii). All the patients had been living in the UK for an average of 15 (range 6-24) years, with no known recent exposure to tuberculosis. Five patients are now alive and well, one developed malabsorption following M. kansasii peritonitis, but two with tuberculous peritonitis died before treatment could be instituted. Mycobacterial infections were associated with a high level of mortality and morbidity. No Asian patient developed mycobacterial infection during post-transplant immunosuppressive therapy in the study period, probably because of the routine anti-tuberculous chemoprophylaxis employed in this group of patients. The diagnosis of mycobacterial infection should be suspected when an Asian dialysis patient develops a pyrexia of unknown origin. It is likely, though not proven, that anti-tuberculous chemoprophylaxis might reduce this high incidence of tuberculous infection in Asian dialysis patients.     

An investigation of clinical and immunological events following repeated aerodigestive tract challenge infections with live Mycobacterium bovis Bacille Calmette Guérin

Bacille Calmette Guérin substrain Moreau Rio de Janeiro is an attenuated strain of Mycobacterium bovis that has been used extensively as an oral tuberculosis vaccine. We assessed its potential as a challenge model to study clinical and immunological events following repeated mycobacterial gut infection. Seven individuals received three oral challenges with approximately 10⁷ viable bacilli. Clinical symptoms, T-cell responses and gene expression patterns in peripheral blood were monitored. Clinical symptoms were relatively mild and declined following each oral challenge. Delayed T-cell responses were observed, and limited differential gene expression detected by microarrays. Oral challenge with BCG Moreau Rio de Janeiro vaccine was immunogenic in healthy volunteers, limiting its potential to explore clinical innate immune responses, but with low reactogenicity.     

Control of mycobacteriosis in zebrafish (Danio rerio) mucosally vaccinated with heat-inactivated Mycobacterium bovis

BackgroundMycobacterial infections greatly affect human and animal health worldwide, and vaccines are effective, sustainable and economic interventions for the prevention and control of these infectious diseases. Recent results support the use of zebrafish as a model for studying the pathophysiology of mycobacterial infection and for the development of novel interventions for tuberculosis (TB) control. Recently, we showed that oral immunization with the heat-inactivated M. bovis vaccine (M. bovis IV) protect wild boar against TB, and suggested that this vaccine may controls mycobacterial infection in other species.MethodsIn this study we evaluated the effect of M. bovis IV on the control of mycobacteriosis in zebrafish mucosally vaccinated by immersion and challenged intraperitoneally with Mycobacterium marinum.ResultsThe results showed that the M. bovis IV administered by immersion protected zebrafish against mycobacteriosis caused by M. marinum by reduction in mycobacterial infection, the number of mycobacteria per granuloma and the number of granulomas per fish. An IgM antibody response against M. bovis antigens was developed in vaccinated fish. Evidences suggested that the protective mechanism elicited by mucosal vaccination with M. bovis IV in zebrafish was based on the activation of the innate immune response through the C3 pathway.ConclusionsThese results support the use of the M. bovis IV administered by immersion for the control of mycobacteriosis in fish.     

Anti-cytokine therapeutics and infections

In view of the increasing use of anti-cytokine-based therapies to treat autoimmune diseases, the role of specific cytokines in host defense against infection has become a highly relevant area of investigation. There are over 300,000 patients worldwide being treated with agents that specifically block the biological activities of interleukin-1 (IL-1) or tumor necrosis factor (TNF) for reducing the severity of autoimmune diseases such as rheumatoid arthritis, Crohn's disease or psoriasis. Those patients receiving anti-TNF-alpha or IL-1 blocking therapies are treated on a chronic basis. Studies suggest that other chronic inflammatory diseases will benefit from anti-cytokine therapies. However, there is a growing body of clinical evidence that neutralization of TNF-alpha is associated with an increased risk of opportunistic infections, including mycobacterial diseases. Blockade of IL-1 activity with the IL-1 receptor antagonist (IL-1Ra) appears, at present, to be relatively safe. However, because of physician under reporting (some estimates of reporting being less than 5% of these infections), the true incidence of infections, both serious and non-serious, will remain unknown. Does the increase in infections associated with anti-cytokine-based therapies come as a surprise? Of the two components of host defense, the innate and the acquired responses, which are affected by anti-cytokine therapies? From a wealth of rodent studies using live infection models, the following conclusions can be drawn: (1) neutralization or gene deletion for TNF-alpha is frequently associated with reduction of host defense in models of live Gram-positive or Gram-negative infections as well as infection by intracellular microbes such as Salmonella and Listeria; (2) absence of the IL-1 receptor can also result in decreased resistance to Listeria or Gram-positive bacteria and (3) TNF-alpha and IFN-gamma are required for defense against infection caused by Mycobacterium tuberculosis.     

A practical approach to tuberculosis diagnosis and treatment in liver transplant recipients in a low-prevalence area

Solid organ transplant candidates/recipients are at risk of mycobacterial infections. Although guidelines on the management of latent tuberculosis infection and active tuberculosis are available for solid organ transplant recipients, limited guidance focuses on end-stage liver disease or liver transplant recipients who require management in a referral center. Therapeutic challenges arise from direct antituberculosis drug-related hepatotoxicity, and substantial metabolic interactions between immunosuppressive and antituberculosis drugs. Another issue is the optimal timing of therapy with regards to the time of transplantation. This review focuses on the importance of tuberculosis screening with immunological tests, challenges in the diagnosis, management, and treatment of latent tuberculosis infection and active tuberculosis, as well as risk assessment for active tuberculosis in the critical peri-liver transplantation period. We detail therapeutic adjustments required for the management of antituberculosis drugs in latent tuberculosis infection and active tuberculosis, particularly when concomitantly using rifampicin and immunosuppressive drugs.     

Indications for,and the significance of,the tuberculin test in the Netherlands

The almost 100-year-old tuberculin skin test still is the gold standard for diagnosing Mycobacterium tuberculosis infection. The sensitivity of this test with the usual cut-off values is high, but may be decreased with impaired cellular immunity and at older age. The specificity is primarily determined by cross-reactivity to atypical mycobacterial infections and vaccination with Bacillus Calmette-Guérin (BCG). Positivity of the skin test after BCG vaccination decreases with time after vaccination and depends on the age when vaccinated. The tuberculin reaction can be boosted by repeated tuberculin skin tests over a short time period, whereby the anamnestic immune response is stimulated. This boosting phenomenon occurs mostly with atypical mycobacterial infections, after BCG vaccination and at older age. Interpretation of the tuberculin skin test depends on the indication for the test, the expected risk of latent tuberculosis infection, higher prevalence of 'old' tuberculosis in elderly Dutch people and immigrants, BCG vaccination status and, if a baseline value is available, the boosting phenomenon. Its role in the diagnosis of tuberculosis is limited.     

Disseminated infection with Simiae-Avium group mycobacteria in persons with AIDS--Thailand and Malawi, 1997

Persons with advanced human immunodeficiency virus (HIV)-1 infection are susceptible to disseminated mycobacterial infections. In the United States, most such infections are caused by Mycobacterium avium or M. intracellulare (i.e., M. avium complex [MAC]). In less developed countries, M. tuberculosis is equally or more prevalent than MAC in persons with HIV-1 infection. Other mycobacterial species have been reported to cause disseminated infection in HIV-infected persons, including Simiae-Avium (SAV) group mycobacteria. SAV group organisms share characteristics of M. avium and M. simiae. Although disseminated (i.e., the isolation of a mycobacterial species from the blood) infection with M. simiae has been reported in HIV-infected persons, another distinct species within the SAV group, M. triplex, was characterized in 1996. Two cases of disseminated infection caused by M. triplex have been reported in HIV-1-positive persons. This report describes four HIV-infected patients from Bangkok, Thailand, and Lilongwe, Malawi, who were infected with SAV group organisms. Because different mycobacterial species are not susceptible uniformly to antimycobacterial agents, accurate identification of mycobacterial species causing an infection is crucial for directing appropriate therapy.