Mechanisms of leucocyte recruitment to the inflamed large intestine: redundancy in integrin and addressin usage
Mechanisms of leucocyte recruitment to the inflamed large intestine: redundancy in integrin and addressin usage
复制标题
DOI：
10.1111/j.1365-3024.2007.01017.x
复制
发表时间：
2008-03-01
影响因子：
2.2
通讯作者：
Else, K. J.
中科院分区：
文献类型：
--
作者：
Bell, L. V.;Else, K. J.
盲肠线虫毛虫提供了人类鞭虫感染的自然模型。对鼠毛虫的抵抗力取决于宿主 Th2 反应，CD4(+) Th2 细胞迁移到肠道相关淋巴组织 (GALT) 以引发寄生虫排出。因此，CD4(+) T细胞在感染过程中会与其他对寄生虫排出不重要的白细胞亚群（例如嗜酸性粒细胞）一起浸润盲肠固有层。白细胞向 GALT 的运输已被证明依赖于 alpha(4)beta(7)/MAdCAM-1 整合素-地址蛋白相互作用。然而，在存在炎症的情况下，例如在鼠毛虫感染期间，除了传统的肠道归巢相互作用之外，还可能发生白细胞募集的冗余机制。我们利用抗整合素/地址蛋白抗体治疗方案来研究抗性、鼠毛虫感染的 C57BL/6 小鼠中的这种冗余。当仅阻断α(4)β(7)/MAdCAM-1相互作用时，小鼠仍然对鼠毛虫感染具有抵抗力，产生Th2反应，并且CD4(+) T细胞和嗜酸性粒细胞都浸润到感染部位。然而，在缺乏可用的 α(4)β(7) 和 α(4)β(1) 的情况下，小鼠会慢性感染鼠毛虫，并产生更偏向 Th1 的免疫反应。有趣的是，CD4(+) T 细胞（而非嗜酸性粒细胞）能够浸润盲肠，在感染过程中显示出白细胞亚群之间不同程度的冗余。
The caecal-dwelling nematode Trichuris muris provides a natural model of human whipworm infection. Resistance to T. muris is dependent on a host Th2 response, and CD4(+) Th2 cells migrate to the gut-associated lymphoid tissue (GALT) to elicit parasite expulsion. Thus, CD4(+) T cells infiltrate the caecal lamina propria during infection, along with other leucocyte subsets that are not critical for parasite expulsion, such as eosinophils. Trafficking of leucocytes to the GALT has been shown to be dependent on the alpha(4)beta(7)/MAdCAM-1 integrin-addressin interaction. However, where inflammation is present, such as during T. muris infection, redundant mechanisms of leucocyte recruitment may also occur in addition to traditional gut-homing interactions. We utilized an anti-integrin/addressin antibody treatment regime to investigate this redundancy in resistant, T. muris-infected C57BL/6 mice. Where only the alpha(4)beta(7)/MAdCAM-1 interaction was blocked, mice remained resistant to T. muris infection, making a Th2 response and both CD4(+) T cells and eosinophils infiltrated the site of infection. However, in the absence of available alpha(4)beta(7) and alpha(4)beta(1), mice became chronically infected with T. muris and mounted a more Th1-biased immune response. Interestingly, CD4(+) T cells, but not eosinophils, were able to infiltrate the caecum, showing different levels of redundancy between leucocyte subsets during infection.