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用抗结核分枝杆菌多克隆抗体进行的被动血清疗法可预防SCID小鼠化疗后结核感染的复发。

Passive serum therapy with polyclonal antibodies against Mycobacterium tuberculosis protects against post-chemotherapy relapse of tuberculosis infection in SCID mice.

作者信息

Guirado Evelyn, Amat Isabel, Gil Olga, Díaz Jorge, Arcos Virginia, Caceres Neus, Ausina Vicenç, Cardona Pere-Joan

机构信息

Unitat de Tuberculosi Experimental, Department of Microbiology, Fundació Institut per a la Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Crta del Canyet s/n, 08916 Badalona, Catalonia, Spain.

出版信息

Microbes Infect. 2006 Apr;8(5):1252-9. doi: 10.1016/j.micinf.2005.12.004. Epub 2006 Jan 27.

Abstract

We investigated the protective role of immune-sera against reactivation of Mycobacterium tuberculosis infection in SCID mice and found that passive immunization with sera obtained from mice treated with detoxified M. tuberculosis extracts (delivered in liposomes in a composition known as RUTI) exerted significant protection. Our SCID mouse model consisted of aerosol infection by M. tuberculosis, followed by 3 to 8weeks of chemotherapy with isoniazid+rifampicin (INH+RIF) (25 and 10mg/kg, respectively). After infection and antibiotic administration, two groups of mice were treated for up to 10weeks with intraperitoneal passive immunization using hyperimmune serum (HS) obtained from mice infected with M. tuberculosis, treated with chemotherapy (INH+RIF) for 8weeks and inoculated with RUTI (HS group) or with normal serum (CT group). Significant differences were found between HS and CT groups in the number of bacilli in the lungs (3.68+/-2.02 vs. 5.72+/-1.41log(10) c.f.u.), extent of pulmonary granulomatomous infiltration (10.33+/-0.67 vs. 31.2+/-1.77%), and percentage of animals without pulmonary abscesses (16.7% vs. 45.5%). These data strongly suggest a protective role of specific antibodies against lung dissemination of M. tuberculosis infection.

摘要

我们研究了免疫血清对SCID小鼠结核分枝杆菌感染再激活的保护作用,发现用经解毒的结核分枝杆菌提取物(以脂质体形式递送,组成名为RUTI)处理的小鼠血清进行被动免疫可发挥显著保护作用。我们的SCID小鼠模型包括通过气溶胶感染结核分枝杆菌,随后用异烟肼+利福平(INH+RIF)(分别为25和10mg/kg)进行3至8周的化疗。在感染和抗生素给药后,两组小鼠分别用从感染结核分枝杆菌、接受8周化疗(INH+RIF)并接种RUTI的小鼠获得的超免疫血清(HS组)或正常血清(CT组)进行腹腔被动免疫,持续治疗长达10周。HS组和CT组在肺部杆菌数量(3.68±2.02对5.72±1.41log(10) c.f.u.)、肺部肉芽肿浸润程度(10.33±0.67对31.2±1.77%)以及无肺脓肿动物的百分比(16.7%对45.5%)方面存在显著差异。这些数据强烈表明特异性抗体对结核分枝杆菌感染肺部播散具有保护作用。

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