Accumulation of CD11b+ lung dendritic cells in response to fungal infection results from the CCR2-mediated recruitment and differentiation of Ly-6Chigh monocytes.

Accumulation of CD11b+ lung dendritic cells in response to fungal infection results from the CCR2-mediated recruitment and differentiation of Ly-6Chigh monocytes.
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DOI:
10.4049/jimmunol.0902823
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发表时间:
2009-12-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Toews GB
Toews GB
中科院分区:
其他
文献类型:
--
作者:
Osterholzer JJ;Chen GH;Olszewski MA;Curtis JL;Huffnagle GB;Toews GB

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肺清除率的封装酵母隐球菌的新型与CCR 2介导的肺树突状细胞(DC)的积累和T1适应性免疫反应的发展。本研究的目的是鉴定导致肺DC数量大量增加的循环DC前体。使用已建立的小鼠模型评估CCR 2 +/+小鼠和CCR 2 −/−小鼠在感染C.新人类结果表明,在CCR+/+小鼠的外周血和肺中,Ly-6Chigh单核细胞的数量平行增加,而CD 11 c + MHC II类+前DC在外周血中的流行率低10倍,并且在两种品系之间没有差异。Ly-6Chigh单核细胞的积累与感染的CCR 2 +/+小鼠肺中CD 11b + DC数量的大幅增加相关。体内回收的肺细胞的比较表型分析表明,Ly-6Chigh单核细胞在肺中分化为CD 11b + DC;分化与共刺激分子的上调和Ly-6C表达的降低相关。此外,体外实验证实Ly-6Chigh单核细胞分化为CD 11b + DC。Ly-6Chigh单核细胞和CD 11b + DC的积聚不是由于它们在原位的增殖。我们的结论是CCR 2介导的CD 11b + DC在隐球菌感染小鼠的肺中的积累主要归因于Ly-6Chigh单核细胞的持续募集和分化。
Pulmonary clearance of the encapsulated yeast Cryptococcus neoformans is associated with the CCR2-mediated accumulation of lung dendritic cells (DC) and the development of a T1 adaptive immune response. The objective of this study was to identify the circulating DC precursor(s) responsible for this large increase in lung DC numbers. An established murine model was used to evaluate putative DC precursors in the blood, bone marrow, and lungs of CCR2+/+ mice and CCR2−/− mice throughout a time course following infection with C. neoformans. Results demonstrate that numbers of Ly-6Chigh monocytes increased in parallel in the peripheral blood and lungs of CCR+/+ mice, whereas CD11c+ MHC class II+ pre-DC were 10-fold less prevalent in the peripheral blood and did not differ between the two strains. Accumulation of Ly-6Chigh monocytes correlated with a substantial increase in the numbers of CD11b+ DC in the lungs of infected CCR2+/+ mice. Comparative phenotypic analysis of lung cells recovered in vivo suggests that Ly-6Chigh monocytes differentiate into CD11b+ DC in the lung; differentiation is associated with up-regulation of costimulatory molecules and decreased Ly-6C expression. Furthermore, in vitro experiments confirmed that Ly-6Chigh monocytes differentiate into CD11b+ DC. Accumulation of Ly-6Chigh monocytes and CD11b+ DC was not attributable to their proliferation in situ. We conclude that the CCR2-mediated accumulation of CD11b+ DC in the lungs of Cryptococcus-infected mice is primarily attributable to the continuous recruitment and differentiation of Ly-6Chigh monocytes.
树突状细胞对于维持流感病毒感染小鼠肺部的三级淋巴结构至关重要。
DOI: 10.1084/jem.20090410
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