Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus
Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus
复制标题
DOI：
10.1016/s0002-9440(10)65068-7
复制
发表时间：
2000-06-01
影响因子：
6
通讯作者：
Maeda, N
中科院分区：
文献类型：
--
作者：
Dawson, TC;Beck, MA;Maeda, N
对甲型流感病毒的免疫反应的特点是巨噬细胞和 T 淋巴细胞涌入受感染宿主的肺部，并伴随着许多 CC 趋化因子的诱导表达。 CC趋化因子受体CCR5和CCR2均在活化的巨噬细胞和T细胞上表达。我们通过用小鼠适应的甲型流感病毒株感染 CCR5 缺陷型小鼠和 CCR2 缺陷型小鼠，研究了这些趋化因子受体的缺失如何影响肺趋化因子表达并诱导白细胞招募。 CCR5(-/-)小鼠表现出与急性、严重肺炎相关的死亡率增加，而CCR2(-/-)小鼠由于巨噬细胞募集缺陷而免受流感早期病理表现的影响。 CCR2(-/-)小鼠巨噬细胞积累的延迟导致T细胞迁移的延迟，这与早期时间点的高肺部病毒滴度相关。感染的CCR5(-/-)小鼠和CCR2(-/-)小鼠均表现出MCP-1基因表达增加，MCP-1是CCR2(-/-)的主要配体和诱导巨噬细胞迁移的关键调节因子。这些研究说明了 CCR5 和 CCR2 在巨噬细胞对流感感染的反应中发挥着截然不同的作用，并证明了巨噬细胞募集缺陷如何影响细胞介导的免疫反应的正常发展。
The immune response to influenza A virus is characterized by an influx of both macrophages and T lymphocytes into the lungs of the infected host, accompanied by induced expression of a number of CC chemokines. CC chemokine receptors CCR5 and CCR2 are both expressed on activated macrophages and T cells. We examined how the absence of these chemokine receptors would affect pulmonary chemokine expression and induced leukocyte recruitment by infecting CCR5-deficient mice and CCR2-deficient mice with a mouse-adapted strain of influenza A virus. CCR5(-/-) mice displayed increased mortality rates associated with acute, severe pneumonitis, whereas CCR2(-/-) mice were protected from the early pathological manifestations of influenza because of defective macrophage recruitment. This delay in macrophage accumulation in CCR2(-/-) mice caused a subsequent delay in T cell migration, which correlated with high pulmonary viral titers at early time points. Infected CCR5(-/-) mice and CCR2(-/-) mice both exhibited increased expression of the gene for MCP-1, the major ligand for CCR2(-/-) and a key regulator of induced macrophage migration. These studies illustrate the very different roles that CCR5 and CCR2 play in the macrophage response to influenza infection and demonstrate how defects in macrophage recruitment affect the normal development of the cell-mediated immune response.