Meurens François, Berri Mustapha, Auray Gael, Melo Sandrine, Levast Benoît, Virlogeux-Payant Isabelle, Chevaleyre Claire, Gerdts Volker, Salmon Henri
Institut National de la Recherche Agronomique (INRA), UR1282, Infectiologie Animale et Santé Publique, F-37380 Nouzilly (Tours), France.
Vet Res. 2009 Jan-Feb;40(1):5. doi: 10.1051/vetres:2008043. Epub 2008 Oct 16.
Salmonella enterica subspecies enterica serovar Typhimurium, commonly called S. Typhimurium, can cause intestinal infections in humans and various animal species such as swine. To analyze the host response to Salmonella infection in the pig we used an in vivo gut loop model, which allows the analysis of multiple immune responses within the same animal. Four jejunal gut-loops were each inoculated with 3 x 10(8) cfu of S. Typhimurium in 3 one-month-old piglets and mRNA expressions of various cytokines, chemokines, transcription factors, antimicrobial peptides, toll like and chemokine receptors were assessed by quantitative real-time PCR in the Peyer's patch and the gut wall after 24 h. Several genes such as the newly cloned CCRL1/CCX-CKR were assessed for the first time in the pig at the mRNA level. Pro-inflammatory and T-helper type-1 (Th1) cytokine mRNA were expressed at higher levels in infected compared to non-infected control loops. Similarly, some B cell activation genes, NOD2 and toll like receptor 2 and 4 transcripts were more expressed in both tissues while TLR5 mRNA was down-regulated. Interestingly, CCL25 mRNA expression as well as the mRNA expressions of its receptors CCR9 and CCRL1 were decreased both in the Peyer's patch and gut wall suggesting a potential Salmonella strategy to reduce lymphocyte homing to the intestine. In conclusion, these results provide insight into the porcine innate mucosal immune response to infection with entero-invasive microorganisms such as S. Typhimurium. In the future, this knowledge should help in the development of improved prophylactic and therapeutic approaches against porcine intestinal S. Typhimurium infections.
肠炎沙门氏菌肠道亚种鼠伤寒血清型,通常称为鼠伤寒沙门氏菌,可导致人类和猪等多种动物发生肠道感染。为了分析猪对沙门氏菌感染的宿主反应,我们使用了一种体内肠袢模型,该模型能够在同一动物体内分析多种免疫反应。在3只1月龄仔猪中,给4个空肠肠袢分别接种3×10⁸cfu的鼠伤寒沙门氏菌,24小时后通过定量实时PCR评估派尔集合淋巴结和肠壁中各种细胞因子、趋化因子、转录因子、抗菌肽、Toll样受体和趋化因子受体的mRNA表达。首次在猪中于mRNA水平评估了几个新克隆的基因,如CCRL1/CCX-CKR。与未感染的对照肠袢相比,感染的肠袢中促炎细胞因子和1型辅助性T细胞(Th1)细胞因子的mRNA表达水平更高。同样,一些B细胞活化基因、NOD2以及Toll样受体2和4的转录本在两种组织中表达更多,而TLR5 mRNA表达下调。有趣的是,派尔集合淋巴结和肠壁中CCL25 mRNA表达及其受体CCR9和CCRL1的mRNA表达均降低,这表明鼠伤寒沙门氏菌可能有一种减少淋巴细胞归巢至肠道的策略。总之,这些结果为猪对鼠伤寒沙门氏菌等肠侵袭性微生物感染的先天性黏膜免疫反应提供了见解。未来,这些知识应有助于开发针对猪肠道鼠伤寒沙门氏菌感染的改进预防和治疗方法。