Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
PLoS Negl Trop Dis. 2009;3(3):e403. doi: 10.1371/journal.pntd.0000403. Epub 2009 Mar 31.
Infection with intestinal helminths is common and may contribute to the decreased efficacy of Vibrio cholerae vaccines in endemic compared to non-endemic areas. However, the immunomodulatory effects of concomitant intestinal parasitic infection in cholera patients have not been systematically evaluated.
We evaluated V. cholerae-specific immune responses in a cohort of patients with severe cholera. 361 patients completed 21 days of observation and 53 (15%) had evidence of a concomitant intestinal parasitic infection based on direct microscopy. Although there were no significant differences in the vibriocidal or lipopolysaccharide (LPS)-specific immune responses to V. cholerae, helminth-infected cholera patients had decreased fecal and serum IgA immune responses to the B subunit of cholera toxin (CTB) as well as a more modest decrease in serum IgG response to CTB. These findings remained significant for all classes of helminth infection and when controlling for potential confounding variables such as age and nutritional status. Although we hypothesized the differential effect on CTB and LPS immune responses was due to T-cell-dependent immunomodulatory effects of helminth infection, we did not find additional evidence to support a classic Th1 or Th2 polarization of the immune response to V. cholerae infection related to parasite infection.
CONCLUSIONS/SIGNIFICANCE: The finding that helminth infection has a profound association with the mucosal humoral immune response to V. cholerae has implications for the development of protective immunity in cholera-endemic areas and provides an additional basis for deworming programs in cholera-endemic areas. Additional studies, including further characterization of the role of T cells in the immune response to human V. cholerae infection and the development of an animal model of co-infection, may provide additional insight into the mechanisms underlying these findings.
肠道寄生虫感染很常见,可能会降低霍乱弧菌疫苗在流行地区的效果,而在非流行地区效果则较好。然而,霍乱患者同时存在肠道寄生虫感染的免疫调节作用尚未得到系统评估。
我们评估了严重霍乱患者队列中的霍乱弧菌特异性免疫反应。361 例患者完成了 21 天的观察,其中 53 例(15%)直接显微镜检查证实存在同时发生的肠道寄生虫感染。虽然对霍乱弧菌的杀菌和脂多糖(LPS)特异性免疫反应没有显著差异,但感染寄生虫的霍乱患者粪便和血清 IgA 对霍乱毒素(CTB)B 亚单位的免疫反应降低,对 CTB 的血清 IgG 反应也略有降低。这些发现对于所有类别的寄生虫感染仍然具有统计学意义,并且在控制年龄和营养状况等潜在混杂变量时也是如此。尽管我们假设对 CTB 和 LPS 免疫反应的差异影响是由于寄生虫感染引起的 T 细胞依赖性免疫调节作用,但我们没有发现更多证据支持与寄生虫感染相关的霍乱弧菌感染的免疫反应存在经典的 Th1 或 Th2 极化。
结论/意义:寄生虫感染与霍乱弧菌黏膜体液免疫反应之间存在密切关联,这对霍乱流行地区保护性免疫的发展具有重要意义,并为霍乱流行地区的驱虫计划提供了额外的依据。进一步的研究,包括进一步描述 T 细胞在人类霍乱弧菌感染免疫反应中的作用以及开发共感染的动物模型,可能会为这些发现的机制提供更多的见解。