An immunoregulatory role for neutrophils in CD4+ T helper subset selection in mice with candidiasis.
An immunoregulatory role for neutrophils in CD4+ T helper subset selection in mice with candidiasis.
复制标题
中性粒细胞在念珠菌病小鼠 CD4 T 辅助亚群选择中的免疫调节作用。
作者：
L. Romani;A. Mencacci;E. Cenci;G. D. Sero;F. Bistoni;P. Puccetti
粒细胞可能在感染免疫反应的不同分支中发挥免疫调节和效应作用。利用活疫苗菌株或毒力攻毒白色念珠菌感染小鼠的粘膜或全身感染，我们研究了单克隆抗体介导的中性粒细胞耗竭对初级和次级攻毒过程以及CD4+细胞依赖性免疫发展的影响。我们获得了在所有测试条件下感染时发生的中性粒细胞耗竭的有害影响的证据，无论是在幼稚的还是先前免疫的小鼠中。相反，中性粒细胞耗竭似乎有利于宿主在压倒性的全身感染过程的后期。为了试图将中性粒细胞功能与T细胞反应的性质联系起来，我们测试了中性粒细胞产生细胞因子的能力，这些细胞因子与功能上不同的CD4+ Th细胞对念珠菌的反应相关。我们发现，中性粒细胞在体外被赋予了分泌IL-12和IL-10的能力，以响应酵母。在th1相关的自限性感染过程的早期，中性粒细胞消融似乎改变了T细胞反应的定性发展，并使小鼠易受感染。除了长期公认的急性抗念珠菌反应外，这些数据表明中性粒细胞在念珠菌特异性免疫的启动和表达中都起着重要作用。
Granulocytes may serve immunoregulatory and effector roles in different limbs of the immune response to infection. Using live vaccine strain or virulent challenge in mucosal or systemic infection of mice with Candida albicans, we examined the effect of mAb-mediated depletion of neutrophils on the course of primary and secondary challenge and on development of CD4+ cell-dependent immunity. We obtained evidence of deleterious effects of neutrophil depletion occurring at the time of infection under all conditions of testing, both in naive and in previously immunized mice. In contrast, neutrophil depletion appeared to benefit the hosts late in the course of an overwhelming systemic infection. In an attempt to correlate neutrophil function with the nature of the T cell response, we tested the ability of neutrophils to produce cytokines associated with functionally distinct CD4+ Th cell responses to Candida. We found that neutrophils were endowed with the capacity to secrete IL-12 and IL-10 in vitro in response to the yeast. Neutrophil ablation early in the course of Th1-associated, self-limiting infection appeared to change the qualitative development of the T cell response, and rendered mice susceptible to infection. In addition to long recognized contributions to acute anti-candidal responses, these data suggest an important role for neutrophils both in initiation and in expression of Candida-specific immunity.