Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602, USA.
Vet Res. 2014 Jan 23;45(1):6. doi: 10.1186/1297-9716-45-6.
Vaccines to prevent Trypanosoma cruzi infection in humans or animals are not available, and in many settings, dogs are an important source of domestic infection for the insect vector. Identification of infected canines is crucial for evaluating peridomestic transmission dynamics and parasite control strategies. As immune control of T. cruzi infection is dependent on humoral and cell-mediated immune responses, we aimed to define a serodiagnostic assay and T cell phenotypic markers for identifying infected dogs and studying the canine T. cruzi-specific immune response. Plasma samples and peripheral blood mononuclear cells (PBMCs) were obtained from forty-two dogs living in a T. cruzi-endemic region. Twenty dogs were known to be seropositive and nine seronegative by conventional serologic tests two years prior to our study. To determine canine seroreactivity, we tested sera or plasma samples in a multiplex bead array against eleven recombinant T. cruzi proteins. Ninety-four percent (17/18) of dogs positive by multiplex serology were initially positive by conventional serology. The frequency of IFNγ-producing cells in PBMCs responding to T. cruzi correlated to serological status, identifying 95% of multiplex seropositive dogs. Intracellular staining identified CD4+ and CD8+ T cell populations as the sources of T. cruzi lysate-induced IFNγ. Low expression of CCR7 and CD62L on CD4+ and CD8+ T cells suggested a predominance of effector/effector memory T cells in seropositive canines. These results are the first, to our knowledge, to correlate T. cruzi-specific antibody responses with T cell responses in naturally infected dogs and validate these methods for identifying dogs exposed to T. cruzi.
目前尚无预防人类或动物感染克氏锥虫的疫苗,在许多情况下,狗是传播媒介昆虫的重要家养感染源。鉴定感染犬对于评估家犬传播动力学和寄生虫控制策略至关重要。由于克氏锥虫感染的免疫控制依赖于体液和细胞介导的免疫反应,我们旨在确定一种血清学诊断检测方法和 T 细胞表型标志物,用于鉴定感染犬并研究犬的克氏锥虫特异性免疫反应。从生活在克氏锥虫流行地区的 42 只狗中获得血浆样本和外周血单核细胞(PBMC)。在我们的研究之前两年,通过传统的血清学检测,已知 20 只狗呈血清阳性,9 只狗呈血清阴性。为了确定犬的血清反应性,我们用十一重组克氏锥虫蛋白在多重珠粒阵列中检测血清或血浆样本。94%(17/18)通过多重血清学检测呈阳性的狗最初通过传统血清学检测呈阳性。对 T. cruzi 反应的 PBMC 中产生 IFNγ 的细胞的频率与血清学状态相关,可识别 95%的多重血清阳性犬。胞内染色鉴定 CD4+和 CD8+T 细胞群为 T. cruzi 裂解物诱导 IFNγ的来源。CD4+和 CD8+T 细胞上 CCR7 和 CD62L 的低表达表明在血清阳性犬中效应/效应记忆 T 细胞占主导地位。这些结果是我们首次(据我们所知)将克氏锥虫特异性抗体反应与自然感染犬的 T 细胞反应相关联,并验证了这些方法用于鉴定接触克氏锥虫的犬。