Bonney Kevin M, Taylor Joann M, Thorp Edward B, Epting Conrad L, Engman David M
Liberal Studies, Faculty of Arts and Sciences, New York University, New York, NY, USA.
Parasitol Res. 2015 Mar;114(3):1167-78. doi: 10.1007/s00436-014-4300-3. Epub 2015 Jan 11.
Infection with the protozoan parasite Trypanosoma cruzi may lead to a potentially fatal cardiomyopathy known as Chagas heart disease. This disease is characterized by infiltration of the myocardium by mononuclear cells, including CD4+ T cells, together with edema, myofibrillary destruction, and fibrosis. A multifaceted systemic immune response develops that ultimately keeps parasitemia and tissue parasitosis low. T helper 1 and other pro-inflammatory T cell responses are effective at keeping levels of T. cruzi low in tissues and blood, but they may also lead to tissue inflammation when present chronically. The mechanism by which the inflammatory response is regulated in T. cruzi-infected individuals is complex, and the specific roles that Th17 and T regulatory (Treg) cells may play in that regulation are beginning to be elucidated. In this study, we found that depletion of Treg cells in T. cruzi-infected mice leads to reduced cardiac parasitosis and inflammation, accompanied by an augmented Th1 response early in the course of infection. This is followed by a downregulation of the Th1 response and increased Th17 response late in infection. The effect of Treg cell depletion on the Th1 and Th17 cells is not observed in mice immunized with T. cruzi in adjuvant. This suggests that Treg cells specifically regulate Th1 and Th17 cell responses during T. cruzi infection and may also be important for modulating parasite clearance and inflammation in the myocardium of T. cruzi-infected individuals.
感染原生动物寄生虫克氏锥虫可能会导致一种潜在致命的心肌病，即恰加斯心脏病。这种疾病的特征是单核细胞浸润心肌，包括CD4 + T细胞，同时伴有水肿、肌原纤维破坏和纤维化。会产生多方面的全身免疫反应，最终使寄生虫血症和组织寄生虫感染率保持在低水平。辅助性T细胞1和其他促炎性T细胞反应能有效使组织和血液中的克氏锥虫水平保持在低水平，但长期存在时也可能导致组织炎症。克氏锥虫感染个体中炎症反应的调节机制很复杂，而辅助性T细胞17（Th17）和调节性T（Treg）细胞在该调节中可能发挥的具体作用正开始得到阐明。在本研究中，我们发现克氏锥虫感染小鼠中Treg细胞的耗竭会导致心脏寄生虫感染和炎症减轻，同时在感染过程早期伴有辅助性T细胞1反应增强。随后在感染后期辅助性T细胞1反应下调，辅助性T细胞17反应增加。在用佐剂中的克氏锥虫免疫的小鼠中未观察到Treg细胞耗竭对辅助性T细胞1和辅助性T细胞17细胞的影响。这表明Treg细胞在克氏锥虫感染期间特异性调节辅助性T细胞1和辅助性T细胞17细胞反应，并且对于调节克氏锥虫感染个体心肌中的寄生虫清除和炎症也可能很重要。
