Susceptibility to Vibrio cholerae Infection in a Cohort of Household Contacts of Patients with Cholera in Bangladesh
Susceptibility to Vibrio cholerae Infection in a Cohort of Household Contacts of Patients with Cholera in Bangladesh
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DOI：
10.1371/journal.pntd.0000221
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发表时间：
2008-04-01
影响因子：
3.8
通讯作者：
Calderwood, Stephen B.
中科院分区：
文献类型：
--
作者：
Harris, Jason B.;LaRocque, Regina C.;Calderwood, Stephen B.
背景：尽管最近在了解霍乱弧菌致病的分子基础方面取得了进展，但对决定人类对霍乱弧菌感染易感性差异的因素知之甚少。方法和结果：我们对孟加拉国霍乱患者的家庭接触者进行了一项观察性研究，并比较了感染培养阳性霍乱弧菌的家庭成员和未感染霍乱弧菌的家庭成员的基线特征。虽然杀弧性抗体是先前描述的唯一与保护霍乱弧菌感染相关的免疫学标志物，但我们发现，霍乱弧菌三种抗原-霍乱毒素B亚单位、脂多糖和毒素共同调节菌毛的主要成分TCPA-特异性的血清IgA水平也预测了感染O1霍乱弧菌的家庭接触患者的保护作用。O1霍乱弧菌是目前霍乱的主要原因。循环中的TCPA IgA抗体也与预防O139霍乱弧菌感染有关。相反，血清中针对这三种抗原的抗体与对任一种血清群感染的保护之间没有关联。我们还发现了宿主遗传特征和血清视黄醇水平改变霍乱弧菌感染易感性的证据。结论：我们观察到针对某些霍乱弧菌抗原的血清IgA水平(而不是血清免疫球蛋白G)水平与预防感染有关，这突显了更好地了解抗霍乱弧菌的必要性。霍乱菌在粘膜表面的免疫力。此外，我们的数据表明，霍乱弧菌感染的易感性是由免疫学、营养和遗传特征共同决定的；影响霍乱易感性的其他因素仍未确定。
Background: Despite recent progress in understanding the molecular basis of Vibrio cholerae pathogenesis, there is relatively little knowledge of the factors that determine the variability in human susceptibility to V. cholerae infection.Methods and Findings: We performed an observational study of a cohort of household contacts of cholera patients in Bangladesh, and compared the baseline characteristics of household members who went on to develop culture-positive V. cholerae infection with individuals who did not develop infection. Although the vibriocidal antibody is the only previously described immunologic marker associated with protection from V. cholerae infection, we found that levels of serum IgA specific to three V. cholerae antigens-the B subunit of cholera toxin, lipopolysaccharide, and TcpA, the major component of the toxin-co-regulated pilus-also predicted protection in household contacts of patients infected with V. cholerae O1, the current predominant cause of cholera. Circulating IgA antibodies to TcpA were also associated with protection from V. cholerae O139 infection. In contrast, there was no association between serum IgG antibodies specific to these three antigens and protection from infection with either serogroup. We also found evidence that host genetic characteristics and serum retinol levels modify susceptibility to V. cholerae infection.Conclusions: Our observation that levels of serum IgA (but not serum IgG) directed at certain V. cholerae antigens are associated with protection from infection underscores the need to better understand anti-V. cholerae immunity at the mucosal surface. Furthermore, our data suggest that susceptibility to V. cholerae infection is determined by a combination of immunologic, nutritional, and genetic characteristics; additional factors that influence susceptibility to cholera remain unidentified.