Divergent immunomodulating effects of probiotics on T cell responses to oral attenuated human rotavirus vaccine and virulent human rotavirus infection in a neonatal gnotobiotic piglet disease model.
Divergent immunomodulating effects of probiotics on T cell responses to oral attenuated human rotavirus vaccine and virulent human rotavirus infection in a neonatal gnotobiotic piglet disease model.
复制标题
DOI：
10.4049/jimmunol.1300678
复制
发表时间：
2013-09-01
期刊：
影响因子：
--
通讯作者：
Saif LJ
中科院分区：
文献类型：
--
作者：
Chattha KS;Vlasova AN;Kandasamy S;Rajashekara G;Saif LJ
轮状病毒（RV）是儿童腹泻的主要原因。目前的口服疫苗在最需要疫苗的贫困国家无效。因此，迫切需要可负担得起的替代战略。益生菌可以缓解儿童腹泻，并增强特异性全身和粘膜Ab反应，但T细胞反应尚不明确。在这项研究中，我们阐明了T细胞和细胞因子对减毒人RV（AttHRV）和强毒人RV（HRV）的反应，这些猪用益生菌（鼠李糖乳杆菌菌株GG [LGG]和乳酸双歧杆菌Bb 12 [Bb 12]）定植，模拟母乳喂养婴儿的肠道蠕动。新生无菌猪是唯一易患HRV腹泻的动物模型。与未定植和未接种疫苗的猪（对照组）相比，益生菌定植和未接种疫苗（益生菌）的猪在攻毒后腹泻和病毒脱落减少。益生菌组的较高保护与激发前后较高的回肠T调节细胞（TCFs），以及激发后较高的血清TGF-β和较低的血清和胆汁促炎细胞因子相一致。与未定植的接种猪（Vac）相比，接种猪中的益生菌定植增强了先天性血清IFN-α、脾脏和循环产生IFN-γ的T细胞以及血清Th 1细胞因子，但降低了血清Th 2细胞因子。因此，LGG+ Bb 12诱导口服AttHRV疫苗的全身性Th 1免疫刺激作用，与Vac + Pro相比，Vac+Pro攻毒后腹泻严重程度降低，病毒脱落减少。攻毒后，在接种组中诱导了先前未报告的肠道CD 8 T细胞亚群。因此，益生菌LGG+ Bb 12发挥不同的免疫调节作用，对口服AttHRV疫苗具有增强的Th 1应答，而对强毒HRV诱导Treg应答。
Rotaviruses (RVs) are a leading cause of childhood diarrhea. Current oral vaccines are not effective in impoverished countries where the vaccine is needed most. Therefore, alternative affordable strategies are urgently needed. Probiotics can alleviate diarrhea in children and enhance specific systemic and mucosal Ab responses, but the T cell responses are undefined. In this study, we elucidated the T cell and cytokine responses to attenuated human RV (AttHRV) and virulent human RV (HRV) in gnotobiotic pigs colonized with probiotics (Lactobacillus rhamnosus strain GG [LGG] and Bifidobacterium lactis Bb12 [Bb12]), mimicking gut commensals in breastfed infants. Neonatal gnotobiotic pigs are the only animal model susceptible to HRV diarrhea. Probiotic colonized and nonvaccinated (Probiotic) pigs had lower diarrhea and reduced virus shedding postchallenge compared with noncolonized and nonvaccinated pigs (Control). Higher protection in the Probiotic group coincided with higher ileal T regulatory cells (Tregs) before and after challenge, and higher serum TGF-β and lower serum and biliary proinflammatory cytokines postchallenge. Probiotic colonization in vaccinated pigs enhanced innate serum IFN-α, splenic and circulatory IFN-γ−producing T cells, and serum Th1 cytokines, but reduced serum Th2 cytokines compared with noncolonized vaccinated pigs (Vac). Thus, LGG+Bb12 induced systemic Th1 immunostimulatory effects on oral AttHRV vaccine that coincided with lower diarrhea severity and reduced virus shedding postchallenge in Vac+Pro compared with Vac pigs. Previously unreported intestinal CD8 Tregs were induced in vaccinated groups postchallenge. Thus, probiotics LGG+Bb12 exert divergent immunomodulating effects, with enhanced Th1 responses to oral AttHRV vaccine, whereas inducing Treg responses to virulent HRV.
登录
查看更多内容
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
DOI：
10.1128/cdli.10.6.995-1001.2003
发表时间：
2003-11-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Jiang, B;Snipes-Magaldi, L;Glass, RI
通讯作者：
Glass, RI
影响因子：
5.4
作者：
Azevedo, MSP;Yuan, L;Saif, LJ
通讯作者：
Saif, LJ
影响因子：
4.4
作者：
Kaji, Rumi;Kiyoshima-Shibata, Junko;Shida, Kan
通讯作者：
Shida, Kan
DOI：
10.4049/jimmunol.0900995
发表时间：
2009-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Crowe CR;Chen K;Pociask DA;Alcorn JF;Krivich C;Enelow RI;Ross TM;Witztum JL;Kolls JK
通讯作者：
Kolls JK