Antigen-Specific Memory B-cell Responses to Enterotoxigenic Escherichia coli Infection in Bangladeshi Adults
Antigen-Specific Memory B-cell Responses to Enterotoxigenic Escherichia coli Infection in Bangladeshi Adults
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DOI：
10.1371/journal.pntd.0002822
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发表时间：
2014-04-01
影响因子：
3.8
通讯作者：
Qadri, Firdausi
中科院分区：
文献类型：
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作者：
Alam, Mohammad Murshid;Aktar, Amena;Qadri, Firdausi
背景多种肠出血性大肠杆菌的多重感染。大肠杆菌（ETEC）菌株导致针对ETEC腹泻的广谱保护。然而，对ETEC感染的确切保护机制仍不清楚。因此，记忆B细胞的反应和亲和力成熟的抗体的特定ETEC antigens可能是重要的了解机制的protection.MethodologyIn这项研究中，我们调查了热不稳定毒素B亚基（LTB）和定植因子抗原（CFA/I和CS6）的特异性伊加和IgG的记忆B细胞反应在孟加拉国的成年人（n = 52）谁感染了ETEC。我们还调查了伊加和IgG抗体的亲和力，感染后这些antigens.Principal FindingsPatients感染ETEC表达LT或LT+热稳定毒素（ST）和CFA/I组或CS6定植因子开发LTB，CFA/I或CS6特异性记忆B细胞反应在感染后30天。类似地，这些患者在第7天产生针对LTB、CFA/I或CS6的高亲合力伊加和IgG抗体，当与这些特异性抗体在感染急性期（第2天）的亲合力相比时，其在第30天保持显著升高。对CFA/I的记忆B细胞应答、抗体亲合力和其他免疫应答不仅在表达CFA/I的ETEC感染的患者中产生，而且在表达CFA/I交叉反应表位的ETEC感染的患者中也产生。我们还检测到LTB的显著正相关，CFA/I和CS6特异性记忆B细胞应答与相应的抗体亲合力增加。结论本研究表明，ETEC的自然感染诱导记忆B细胞和高亲合力抗体对LTB和定植因子CFA/I和CS6抗原，可以介导记忆反应的再感染。ETEC的暴露，并可能有助于理解的要求，设计一个有效的疫苗接种strategies.Author SummaryEnterogenic Escherichia coli（ETEC）是一种非侵入性病原体引起腹泻的儿童以及成人和旅行者在发展中国家。在使用定殖因子定殖肠道后，生物体分泌热稳定（ST）和/或热不稳定（LT）肠毒素以引起水样腹泻。ETEC的自然感染提供了对后续感染的保护;然而，确切的机制尚不清楚。在这项研究中，我们发现感染ETEC的成人腹泻患者产生毒素（LTB）和定植因子（CFA/I和CS6）特异性记忆B细胞应答以及高度亲合力的抗原特异性抗体。抗体亲合力指数显示与记忆B细胞应答正相关，表明这些过程可能同时发生。这项研究鼓励进一步评估儿童和接种者的这种反应。
BackgroundMultiple infections with diverse enterotoxigenic E. coli (ETEC) strains lead to broad spectrum protection against ETEC diarrhea. However, the precise mechanism of protection against ETEC infection is still unknown. Therefore, memory B cell responses and affinity maturation of antibodies to the specific ETEC antigens might be important to understand the mechanism of protection.MethodologyIn this study, we investigated the heat labile toxin B subunit (LTB) and colonization factor antigens (CFA/I and CS6) specific IgA and IgG memory B cell responses in Bangladeshi adults (n = 52) who were infected with ETEC. We also investigated the avidity of IgA and IgG antibodies that developed after infection to these antigens.Principal FindingsPatients infected with ETEC expressing LT or LT+heat stable toxin (ST) and CFA/I group or CS6 colonization factors developed LTB, CFA/I or CS6 specific memory B cell responses at day 30 after infection. Similarly, these patients developed high avidity IgA and IgG antibodies to LTB, CFA/I or CS6 at day 7 that remained significantly elevated at day 30 when compared to the avidity of these specific antibodies at the acute stage of infection (day 2). The memory B cell responses, antibody avidity and other immune responses to CFA/I not only developed in patients infected with ETEC expressing CFA/I but also in those infected with ETEC expressing CFA/I cross-reacting epitopes. We also detected a significant positive correlation of LTB, CFA/I and CS6 specific memory B cell responses with the corresponding increase in antibody avidity.ConclusionThis study demonstrates that natural infection with ETEC induces memory B cells and high avidity antibodies to LTB and colonization factor CFA/I and CS6 antigens that could mediate anamnestic responses on re-exposure to ETEC and may help in understanding the requirements to design an effective vaccination strategies.Author SummaryEnterotoxigenic Escherichia coli (ETEC) is a non-invasive pathogen causing diarrhea in children as well as in adults and travelers in developing countries. After colonizing the intestine using colonization factors, the organisms secrete heat-stable (ST) and/or heat-labile (LT) enterotoxin to cause watery diarrhea. Natural infection with ETEC provides protection against subsequent infection; however, the precise mechanism is unknown. In this study, we have shown that adult patients with diarrhea infected with ETEC develop toxin (LTB) and colonization factor (CFA/I and CS6) specific memory B cell responses as well as highly avid antigen-specific antibodies. The antibody avidity indices were shown to be positively associated with memory B cell responses, suggesting that these processes may occur in concert. This study encourages further evaluation of such responses in children as well as in vaccinees.