International Centre for Diarrheal Disease Research, Dhaka, Bangladesh.
Infect Immun. 2010 May;78(5):2117-24. doi: 10.1128/IAI.01426-09. Epub 2010 Feb 22.
Vibrio cholerae O1 and enterotoxigenic Escherichia coli (ETEC) are major bacterial pathogens that cause dehydrating disease requiring hospitalization of children and adults. The cholera toxin (CT) produced by V. cholerae O1 and the heat-labile toxin (LT) and/or heat-stable toxin (ST) of ETEC are responsible for secretory diarrhea. We have observed that about 13% of hospitalized diarrheal patients are concomitantly infected with V. cholerae O1 and ETEC. In order to understand the outcome of such dual infections on the clinical and immunological responses in cholera patients, we studied patients infected with V. cholerae O1 (group VC; n = 25), those infected with both V. cholerae O1 and ETEC (group VCET; n = 25), and those infected with ETEC only (group ET; n = 25). The VCET group showed more severe dehydration and had a higher intake of intravenous fluid and more vomiting than the ETEC group (P = 0.01 to 0.003). The VCET patients showed higher vibriocidal responses and increased antibody titers to cholera toxin and lipopolysaccharide (LPS) in plasma than did the V. cholerae O1 patients (P = 0.02 to <0.001). All responses in the V. cholerae O1 and in the VCET groups were more robust than those seen in the group infected with ETEC only (P = 0.01 to <0.001). We thus show that concomitant colonization with ETEC induces immune responses to V. cholerae antigens that are more robust than those seen with V. cholerae O1 infection alone. It is possible that LT or other factors expressed by ETEC may play a role as a mucosal adjuvant in enhancing the immune responses to V. cholerae O1.
霍乱弧菌 O1 和肠产毒性大肠杆菌 (ETEC) 是引起需要住院治疗的儿童和成人脱水性疾病的主要细菌病原体。霍乱弧菌 O1 产生的霍乱毒素 (CT) 和 ETEC 的不耐热毒素 (LT) 和/或热稳定毒素 (ST) 负责分泌性腹泻。我们观察到,约 13%的住院腹泻患者同时感染霍乱弧菌 O1 和 ETEC。为了了解这种双重感染对霍乱患者临床和免疫反应的结果,我们研究了感染霍乱弧菌 O1 的患者(组 VC;n = 25)、同时感染霍乱弧菌 O1 和 ETEC 的患者(组 VCET;n = 25)以及仅感染 ETEC 的患者(组 ET;n = 25)。VCET 组比 ETEC 组表现出更严重的脱水,需要更多的静脉补液和更多的呕吐(P = 0.01 至 0.003)。VCET 患者比霍乱弧菌 O1 患者表现出更高的杀菌反应和对霍乱毒素和脂多糖 (LPS) 的抗体滴度升高(P = 0.02 至 <0.001)。在 V. cholerae O1 和 VCET 组中观察到的所有反应都比仅感染 ETEC 的组中观察到的反应更强烈(P = 0.01 至 <0.001)。因此,我们表明,同时定植 ETEC 会诱导针对霍乱弧菌抗原的免疫反应,比单独感染霍乱弧菌 O1 更强烈。LT 或 ETEC 表达的其他因素可能作为黏膜佐剂发挥作用,增强对霍乱弧菌 O1 的免疫反应。