Differential early interactions between Salmonella enterica serovar typhi and two other pathogenic Salmonella serovars with intestinal epithelial cells
Differential early interactions between Salmonella enterica serovar typhi and two other pathogenic Salmonella serovars with intestinal epithelial cells
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DOI：
10.1128/iai.66.5.2310-2318.1998
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发表时间：
1998-05-01
影响因子：
3.1
通讯作者：
Metcalf, ES
中科院分区：
文献类型：
--
作者：
Weinstein, DL;O'Neill, BL;Metcalf, ES
伤寒沙门氏菌（Salmonella enterica serovar Typhi）（以下简称S.伤寒）是一种宿主限制性病原体，其粘附并侵入回肠末端，随后传播引起人类伤寒。然而，S.伤寒对小动物似乎没有毒性。与此相反，其他致病性沙门氏菌，如S。肠道血清型鼠伤寒和都柏林（S.鼠伤寒沙门氏菌和S.都柏林），通常在人类中引起局部胃肠炎，但已被用作伤寒的模型，因为这些生物体在易感啮齿动物中引起类似于人类伤寒的疾病。在体内，S.伤寒已被证明附着并侵入鼠M细胞，但能迅速从派伊尔氏斑清除而不破坏hi细胞。S.鼠伤寒沙门氏菌伴随着这些M细胞的破坏和随后上皮的脱落。这些数据进一步证实了我们的观点，即伤寒沙门氏菌和非伤寒沙门氏菌血清型的发病机制的早期步骤是不同的。为了扩展这一概念，我们利用体外模型来评估初始宿主-病原体相互作用的三个参数：三种沙门氏菌血清型对人和鼠小肠上皮细胞（IEC）系的粘附，这些沙门氏菌侵入IEC的能力，以及细菌在这些细胞系中诱导白细胞介素-6（IL-6）的能力作为宿主细胞活化和宿主急性期应答的量度。伤寒杆菌对人小IEC的粘附和侵袭能力强于沙门氏菌。鼠伤寒沙门氏菌或S.都柏林有趣的是，S.伤寒不像沙门氏菌，既不能粘附也不能侵入IEC。typhimurium invA anal invE突变体粘附于bent不能侵入IEC，S.伤寒杆菌在人小IEC系中也比其它两种沙门氏菌血清型中的任一种诱导显著更大量的IL-6。这些研究结果表明，不同的宿主细胞因子对细菌病原体的反应可能在感染后的病理后遗症中发挥重要作用。重要的是，S。鼠伤寒沙门氏菌确实在鼠IEC中Plot诱导IL-6。自S.鼠伤寒感染小鼠常被用作伤寒模型，这些发现表明，至少在这种情况下，小鼠模型不能反映人类疾病。综上所述，我们的研究表明：（i）显着差异发生在初始步骤的S。伤寒沙门氏菌（S. typhimurium和S.都柏林致病机理;（ii）关于S.从伤寒小鼠模型中得出的伤寒发病机理应保守地解释。
Salmonella enterica serovar Typhi (hereafter referred to as S. typhi) is a host-restricted pathogen that adheres to and invades the distal ileum and subsequently disseminates to cause typhoid fever in humans. However, S. typhi appears to be avirulent in small animals. In contrast, other pathogenic salmonellae, such as S. enterica serovars Typhimurium and Dublin (S. typhimurium and S. dublin, respectively), typically cause localized gastroenteritis in humans hut have been used as models for typhoid fever because these organisms cause a disease in susceptible rodents that resembles human typhoid. In vivo, S. typhi has been demonstrated to attach to and invade murine M cells but is rapidly cleared from the Peyer's patches without destruction of the hi cells. In contrast, invasion of M cells by S. typhimurium is accompanied by destruction of these M cells and subsequently sloughing of the epithelium. These data have furthered our view that the early steps in the pathogenesis of typhoidal and nontyphoidal Salmonella serovars are distinct, To extend this concept, we have utilized an in vitro model to evaluate three parameters of initial host-pathogen interactions: adherence of three Salmonella serovars to human and murine small intestinal epithelial cell (IEC) lines, the capacity of these salmonellae to invade IECs, and the ability of the bacteria to induce interleukin-6 (IL-6) in these cell lines as a measure of host cell activation and the host acute-phase response, The results demonstrate that S. typhi adheres to and invades human small IECs better than either S. typhimurium or S. dublin. Interestingly, invA and invE null mutants of S. typhi are able neither to adhere to nor to invade IECs, unlike S. typhimurium invA anal invE mutants, which adhere to bent cannot invade IECs, S. typhi also induces significantly greater quantities of IL-6 in human small IEC lines than either of the other two Salmonella serovars. These findings suggest that differential host cytokine responses to bacterial pathogens may play an important role in the pathological sequelae that follow infection. Importantly, S. typhimurium did Plot induce IL-6 in murine IECs. Since S. typhimurium infection in mice is often used as a model of typhoid fever, these findings suggest that, at least in this case, the mouse model does not reflect the human disease. Taken together, our studies indicate that (i) marked differences occur in the initial steps of S. typhi, S. typhimurium, and S. dublin pathogenesis, and (ii) conclusions about S. typhi pathogenesis that have been drawn from the mouse model of typhoid fever should be interpreted conservatively.