Traynor T R, Kuziel W A, Toews G B, Huffnagle G B
Pulmonary Division, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
J Immunol. 2000 Feb 15;164(4):2021-7. doi: 10.4049/jimmunol.164.4.2021.
Pulmonary clearance of the encapsulated yeast Cryptococcus neoformans requires the development of T1-type immunity. The objective of this study was to determine the role of CCR2 in leukocyte recruitment and development of T1-type cell-mediated immunity during pulmonary C. neoformans infection. Intratracheal inoculation of C. neoformans into CCR2 knockout (CCR2-/-) mice produced a prolonged pulmonary infection (5000-fold CFU at 6 wk compared with CCR2+/+ mice) and significant dissemination to the spleen and brain (160- and 800-fold greater). In addition, CCR2 deficiency resulted in significantly reduced recruitment of macrophages (weeks 1-3) and CD8+ T cells (weeks 1-2) into the lungs. The immune response in CCR2-/- mice was characterized by chronic pulmonary eosinophilia, crystal deposition in the lungs, pulmonary leukocyte production of IL-4 and IL-5 but not IFN-gamma, lack of anticryptococcal delayed-type hypersensitivity, and high levels of serum IgE. These results demonstrate that expression of CCR2 is required for the development of a T1-type response to C. neoformans infection and lack of CCR2 results in a switch to a T2-type response. Thus, CCR2 plays a critical role in promoting the development of T1- over T2-type immune responses in the lung following cryptococcus infection.
包囊酵母菌新型隐球菌的肺清除需要T1型免疫的发展。本研究的目的是确定CCR2在肺部新型隐球菌感染期间白细胞募集和T1型细胞介导免疫发展中的作用。将新型隐球菌气管内接种到CCR2基因敲除（CCR2-/-）小鼠中会导致肺部感染延长（与CCR2+/+小鼠相比，6周时CFU增加5000倍），并显著扩散至脾脏和大脑（分别增加160倍和800倍）。此外，CCR2缺陷导致巨噬细胞（第1-3周）和CD8+T细胞（第1-2周）向肺部的募集显著减少。CCR2-/-小鼠的免疫反应特征为慢性肺部嗜酸性粒细胞增多、肺部晶体沉积、肺部白细胞产生IL-4和IL-5但不产生IFN-γ、缺乏抗隐球菌迟发型超敏反应以及血清IgE水平升高。这些结果表明，CCR2的表达是对新型隐球菌感染产生T1型反应所必需的，而缺乏CCR2会导致转变为T2型反应。因此，CCR2在促进隐球菌感染后肺部T1型而非T2型免疫反应的发展中起关键作用。
