INTERACTIONS BETWEEN SIMIAN AIDS (SAIDS) & LEPROSY

猿艾滋病 (SAIDS) 之间的相互作用

• 批准号: 6277408
• 负责人: BOBBY J GORMUS
• 金额: $ 8.66万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277408
• 关键词: AIDS; Mammalia; Primates; bacteria; human tissue; immunology; infection; inflammation; lymphatic system; model design /development; nervous system; sexually transmitted diseases; skin; virus

Last year, we reported that seven of eight rhesus monkeys (RM) coinfected with Mycobacterium leprae (ML) and simian immunodeficiency virus (SIV, 8-10 months pre-ML) harbored acid-fast bacilli (AFB) at sites of dermal inoculation and/or at disseminated sites (nasal mucosa) at times of humane sacrifice (up to 270 days post-ML inoculation) due to SIV-induced debilitation or, in one long- term survivor's case, to date over 3 years post-ML inoculation. Detectable AFB were cleared in biopsies of inoculation sites of RM inoculated with ML alone after 63 days postinoculation; these sites have, so far, remained AFB-negative, thereafter. Compared to animals infected with ML alone, RM coinfected with SIV plus ML showed 1) completely suppressed serum antibody responses to ML-specific phenolic-glycolipid-I and to mycobacteria-common lipoarabinomannan antigens, but strong anti-SIV Gp120 antibody responses; 2) impaired sensitization of blood mononuclear cells (MNC) to in vitro recognition of ML-specific antigens in blastogenic stimulation assays; 3) impaired in vitro responses of blood MNC to nonspecific (ConA) blastogenic stimuli and 4) early post-ML inoculation, there was a significant incremental diminution of percentages of blood CD4+CD29+ T-cells in addition to the existing SIV-induced diminished percentages of the CD4+CD29+ subpopulation. A follow-up study last year in groups of 6 RM that is still in progress showed that SIV given at the same time as ML is significantly more lethal than SIV inoculated 2 weeks prior to ML; both of these inoculation procedures are effective in inducing increased susceptibility to leprosy. The immunologic conclusions described above were confirmed in this follow-up, but differences in relative timing of inoculation with the 2 agents result in differing degrees of modification in immune responses to ML antigens. The results indicate that humoral and cellular immune responses to ML antigens are compromised in ML-inoculated RM that are coinfected with SIV and provide an immunologic basis for our demonstration of enhanced ML persistence or leprosy susceptibility in SIV-ML coinfected RM. The data also provide a probable explanation for the inconsistent observation of increased leprosy risk in HIV-positive patients in the field. It is believed that many of the visible (dermal) symptoms of leprosy are the result of the immune response to ML antigens. Since the immunologic response to ML antigens is compromised in AIDS virus-coinfected patients, it is reasonable to assume that leprosy symptoms would be less obvious, on the average, in coinfected patients. Thus, many coinfected patients would be selectively excluded from field studies that depend upon leprosy recognition followed by secondary, correlational studies for virus infection. Such studies would be expected to erroneously conclude

去年，我们报道了八只恒河猴（RM）中的七个 与分枝杆菌麻风病（ML）和猿猴免疫缺陷共同发明 病毒（SIV，8-10个月前ML）在含有酸像杆菌（AFB） 真皮接种和/或在传播部位的位点（鼻腔 粘膜）时有时牺牲（ML后长达270天） 接种）由于SIV引起的衰弱或一段时间内 幸存者的案件，迄今为止ML接种后3年。 可检测 在接种的RM接种位点活检中清除了AFB 接种后63天后单独使用ML；到目前为止，这些网站有 此后仍然是AFB阴性。 与感染的动物相比 单独的ML，与SIV加上ML共同感染的RM完全显示1） 抑制对ML特异性的血清抗体反应 酚糖脂-I和分枝杆菌脂肪酸脂肪脂动蛋白瘤 抗原，但强烈的抗SIV GP120抗体反应； 2）受损 血液单核细胞（MNC）对体外识别的敏化 在胚刺激测定中的ML特异性抗原； 3）受损 血液跨度对非特异性（CONA）胚胎的体外反应 刺激和4）早期接种后接种，有明显的 血液CD4+ CD29+ T细胞百分比的增量减少 除现有的SIV引起的降低百分比 CD4+ CD29+亚群。 去年对6人组的后续研究 仍在进行中的RM表明SIV与 ML比在接种前2周接种的SIV明显更致命 ML;这两种接种程序均有效诱导 增加了麻风病的敏感性。 免疫学结论 在此随访中证实了上述所述，但是 接种的相对时机与两种药物的接种导致不同 对ML抗原的免疫反应的修饰程度。 这 结果表明对ML的体液和细胞免疫反应 抗原在ML接种的RM中被妥协，并与 SIV并为我们的增强证明提供免疫学基础 SIV-ML共感染RM中的ML持久性或麻风病敏感性。 这 数据还为不一致的可能解释 观察HIV阳性患者的麻风病风险增加 场地。 据认为，许多可见的（真皮）症状 麻风病是对ML抗原的免疫反应的结果。 自从 在艾滋病中，对ML抗原的免疫反应受到损害 病毒感染的患者，可以合理地假设麻风病 平均而言，症状不太明显 患者。 因此，许多共同感染的患者将有选择地 从依赖麻风病识别的现场研究中排除 然后进行病毒感染的继发性相关研究。 预计此类研究将错误地得出结论