Barts and the London School of Medicine and Dentistry, Centre for Digestive Diseases, Blizard Institute of Cell and Molecular Science, Queen Mary University of London, London, UK.
Infect Immun. 2011 Apr;79(4):1647-53. doi: 10.1128/IAI.00922-10. Epub 2011 Jan 31.
Cryptosporidiosis is an important diarrheal disease of humans and neonatal livestock caused by Cryptosporidium spp. that infect epithelial cells. Recovery from Cryptosporidium parvum infection in adult hosts involves CD4(+) T cells with a strong Th1 component, but mechanisms of immunity in neonates are not well characterized. In the present investigation with newborn mice, similar acute patterns of infection were obtained in C57BL/6 wild-type (WT) and T and B cell-deficient Rag2(-/-) mice. In comparison with uninfected controls, the proportion of intestinal CD4(+) or CD8(+) T cells did not increase in infected WT mice during recovery from infection. Furthermore, infection in neonatal WT mice depleted of CD4(+) T cells was not exacerbated. Ten weeks after WT and Rag2(-/-) mice had been infected as neonates, no patent infections could be detected. Treatment at this stage with the immunosuppressive drug dexamethasone produced patent infections in Rag2(-/-) mice but not WT mice. Expression of inflammatory markers, including gamma interferon (IFN-γ) and interleukin-12p40 (IL-12p40), was higher in neonatal WT mice than in Rag2(-/-) mice around the peak of infection, but IL-10 expression was also higher in WT mice. These results suggest that although CD4(+) T cells may be important for elimination of C. parvum, these cells are dispensable for controlling the early acute phase of infection in neonates.
隐孢子虫病是一种由隐孢子虫属引起的重要人类和新生家畜腹泻病,感染上皮细胞。在成年宿主中,从微小隐孢子虫感染中恢复涉及具有强烈 Th1 成分的 CD4(+) T 细胞,但新生儿的免疫机制尚未得到很好的描述。在本研究中,对新生小鼠进行了研究,在 C57BL/6 野生型 (WT) 和 T 和 B 细胞缺陷 Rag2(-/-) 小鼠中获得了类似的急性感染模式。与未感染对照相比,在感染 WT 小鼠从感染中恢复期间,肠道 CD4(+) 或 CD8(+) T 细胞的比例没有增加。此外,在感染 WT 小鼠耗尽 CD4(+) T 细胞的情况下,感染不会加重。在 WT 和 Rag2(-/-) 小鼠作为新生儿感染 10 周后,无法检测到明显的感染。在这个阶段用免疫抑制药物地塞米松治疗,在 Rag2(-/-) 小鼠中产生了明显的感染,但在 WT 小鼠中没有。在感染高峰期,WT 小鼠的炎症标志物(包括γ干扰素 (IFN-γ) 和白细胞介素-12p40 (IL-12p40))的表达高于 Rag2(-/-) 小鼠,但 WT 小鼠的 IL-10 表达也更高。这些结果表明,尽管 CD4(+) T 细胞可能对消除微小隐孢子虫很重要,但这些细胞对于控制新生儿感染的早期急性阶段是可有可无的。