Rakotosamimanana Niaina, Raharimanga Vaomalala, Andriamandimby Soa Fy, Soares Jean-Louis, Doherty T Mark, Ratsitorahina Maherisoa, Ramarokoto Herimanana, Zumla Alimuddin, Huggett Jim, Rook Graham, Richard Vincent, Gicquel Brigitte, Rasolofo-Razanamparany Voahangy
Unité des Mycobactéries, Institut Pasteur de Madagascar, Ambatofotsikely BP 1274, Antananarivo 101, Madagascar.
Clin Vaccine Immunol. 2010 Jul;17(7):1094-103. doi: 10.1128/CVI.00049-10. Epub 2010 May 12.
The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop tuberculosis (TB), though many may become latently infected. More precise measurement of the human immune response to M. tuberculosis infection may help us understand this difference and potentially identify those subjects most at risk of developing active disease. Gamma interferon (IFN-gamma) production has been widely used as a proxy marker to study infection and to examine the human immune response to specific M. tuberculosis antigens. It has been suggested that genetically distinct M. tuberculosis strains may invoke different immune responses, although how these differences influence the immune responses and clinical outcome in human tuberculosis is still poorly understood. We therefore evaluated the antigen-specific IFN-gamma production responses in peripheral blood mononuclear cells from two cohorts of subjects recruited in Antananarivo, Madagascar, from 2004 to 2006 and examined the influence of the infecting M. tuberculosis strains on this response. The cohorts were sputum-positive index cases and their household contacts. Clinical strains isolated from the TB patients were typed by spoligotyping. Comparison of the IFN-gamma responses with the spoligotype of the infecting clinical strains showed that "modern" M. tuberculosis strains, like Beijing and Central Asian (CAS) strains, tended to induce lower IFN-gamma responses than "ancient" strains, like East African-Indian (EAI) strains, in index cases and their household contacts. These results suggest that new strains may have evolved to induce a host response different from that of ancient strains. These findings could have important implications in the development of therapeutic and diagnostic strategies.
大多数接触结核分枝杆菌的健康个体不会患结核病（TB），尽管许多人可能会发生潜伏感染。更精确地测量人体对结核分枝杆菌感染的免疫反应可能有助于我们理解这种差异，并有可能识别出最易发生活动性疾病的个体。γ干扰素（IFN-γ）的产生已被广泛用作研究感染以及检测人体对特定结核分枝杆菌抗原免疫反应的替代标志物。有人提出，基因不同的结核分枝杆菌菌株可能引发不同的免疫反应，尽管这些差异如何影响人类结核病的免疫反应和临床结局仍知之甚少。因此，我们评估了2004年至2006年在马达加斯加塔那那利佛招募的两组受试者外周血单核细胞中抗原特异性IFN-γ的产生反应，并研究了感染的结核分枝杆菌菌株对这种反应的影响。这两组受试者分别是痰涂片阳性的索引病例及其家庭接触者。从结核病患者中分离出的临床菌株通过间隔寡核苷酸分型法进行分型。将IFN-γ反应与感染的临床菌株的间隔寡核苷酸分型进行比较，结果显示，在索引病例及其家庭接触者中，“现代”结核分枝杆菌菌株，如北京菌株和中亚（CAS）菌株，往往比“古老”菌株，如东非-印度（EAI）菌株，诱导产生更低的IFN-γ反应。这些结果表明，新菌株可能已经进化到能诱导不同于古老菌株的宿主反应。这些发现可能对治疗和诊断策略的制定具有重要意义。
