Santos M B, de Oliveira D T, Cazzaniga R A, Varjão C S, Dos Santos P L, Santos M L B, Correia C B, Faria D R, Simon M do V, Silva J S, Dutra W O, Reed S G, Duthie M S, de Almeida R P, de Jesus A R
Laboratory of Molecular Biology, Universidade Federal de Sergipe (UFS), Sao Cristovao, Brazil.
Infectious Diseases Research Institute (IDRI), Seattle, WA, USA.
Scand J Immunol. 2017 Jul;86(1):40-49. doi: 10.1111/sji.12558.
It is well established that helper T cell responses influence resistance or susceptibility to Mycobacterium leprae infection, but the role of more recently described helper T cell subsets in determining severity is less clear. To investigate the involvement of Th17 cells in the pathogenesis of leprosy, we determined the immune profile with variant presentations of leprosy. Firstly, IL-17A, IFN-γ and IL-10 were evaluated in conjunction with CD4 T cell staining by confocal microscopy of lesion biopsies from tuberculoid (TT) and lepromatous leprosy (LL) patients. Secondly, inflammatory cytokines were measured by multiplex assay of serum samples from Multibacillary (MB, n = 28) and Paucibacillary (PB, n = 23) patients and household contacts (HHC, n = 23). Patients with leprosy were also evaluated for leprosy reaction occurrence: LR+ (n = 8) and LR- (n = 20). Finally, peripheral blood mononuclear cells were analysed by flow cytometry used to determine the phenotype of cytokine-producing cells. Lesions from TT patients were found to have more CD4 IL-17A cells than those from LL patients. Higher concentrations of IL-17A and IL-1β were observed in serum from PB than MB patients. The highest serum IFN-γ concentrations were, however, detected in sera from MB patients that developed leprosy reactions (MB LR ). Together, these results indicate that Th1 cells were associated with both the PB presentation and also with leprosy reactions. In contrast, Th17 cells were associated with an effective inflammatory response that is present in the PB forms but were not predictive of leprosy reactions in MB patients.
辅助性T细胞反应影响对麻风分枝杆菌感染的抵抗力或易感性,这一点已得到充分证实,但最近描述的辅助性T细胞亚群在决定疾病严重程度方面的作用尚不清楚。为了研究Th17细胞在麻风病发病机制中的作用,我们确定了麻风病不同表现形式的免疫特征。首先,通过对结核样型(TT)和瘤型麻风(LL)患者病变活检组织进行共聚焦显微镜检查,结合CD4 T细胞染色评估白细胞介素-17A(IL-17A)、干扰素-γ(IFN-γ)和白细胞介素-10(IL-10)。其次,通过多重检测法检测多菌型(MB,n = 28)和少菌型(PB,n = 23)患者及家庭接触者(HHC,n = 23)血清样本中的炎性细胞因子。还对麻风病患者的麻风反应发生情况进行了评估:有反应者(LR+,n = 8)和无反应者(LR-,n = 20)。最后,通过流式细胞术分析外周血单个核细胞,以确定产生细胞因子的细胞表型。发现TT患者病变组织中的CD4 IL-17A细胞比LL患者的更多。PB患者血清中IL-17A和IL-1β的浓度高于MB患者。然而,在发生麻风反应的MB患者(MB LR)血清中检测到最高浓度的血清IFN-γ。这些结果共同表明,Th1细胞与PB型麻风及麻风反应均相关。相比之下,Th17细胞与PB型麻风中存在的有效炎症反应相关,但不能预测MB患者的麻风反应。