Expression of Toll-Like Receptor 4 and Downstream Effectors in Selected Cecal Cell Subpopulations of Chicks Resistant or Susceptible to Salmonella Carrier State

Expression of Toll-Like Receptor 4 and Downstream Effectors in Selected Cecal Cell Subpopulations of Chicks Resistant or Susceptible to Salmonella Carrier State
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DOI:
10.1128/iai.00025-11
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发表时间:
2011-08-01
影响因子:
3.1
通讯作者:
Velge, Philippe
Velge, Philippe
中科院分区:
医学2区
文献类型:
--
作者:
Chausse, Anne-Marie;Grepinet, Olivier;Velge, Philippe

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Toll 样受体 4 (TLR4) 可识别革兰氏阴性菌的脂多糖,在小鼠和人类抵抗沙门氏菌感染方面发挥着重要作用。在鸡中,沙门氏菌可能会建立一种载体状态,使细菌能够在宿主生物体中持续存在,而不会引发临床症状。基于细胞形态学参数,我们开发了一种不使用抗体的方法来分离三种盲肠细胞亚群:淋巴细胞、肠细胞和包含多种细胞类型的细胞群。我们分析了对感染肠炎沙门氏菌的携带者状态具有抗性或易感性的自交系雏鸡盲肠亚群中 TLR4、白细胞介素 1 β (IL-1 β)、IL-8、IL-12 和脂多糖诱导的肿瘤坏死因子 α 因子 (LITAF) 的 mRNA 表达。结果表明,雏鸡对携带状态的抵抗与三种细胞亚群稳态时淋巴细胞比例较高、TLR4和IL-8表达水平较高有关,以及携带状态期间淋巴细胞中LITAF表达水平较高有关。与感染的早期阶段相反,携带者状态的特征是感染和未感染动物之间没有主要的细胞募集差异,并且在测量的所有细胞亚群中 TLR4、IL-1β、IL-8、IL-12 和 LITAF 表达没有显着改变。然而,易感品系雏鸡的淋巴细胞中TLR4表达增加,达到与抗性品系感染雏鸡相同的水平。这些观察结果表明,携带者状态的特点是缺乏免疫激活,并强调了在细胞群水平而不是器官水平上工作的兴趣。
Toll-like receptor 4 (TLR4), which recognizes lipopolysaccharide from Gram-negative bacteria, plays a major role in resistance of mice and humans to Salmonella infection. In chickens, Salmonella may establish a carrier state whereby bacteria are able to persist in the host organism without triggering clinical signs. Based on cellular morphological parameters, we developed a method, without using antibodies, to separate three cecal cell subpopulations: lymphocytes, enterocytes, and a population encompassing multiple cell types. We analyzed the mRNA expression of TLR4, interleukin-1 beta (IL-1 beta), IL-8, IL-12, and lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF) in cecal subpopulations of chicks from inbred lines resistant or susceptible to the carrier state infected with Salmonella enterica serovar Enteritidis. The results showed that resistance to the carrier state in chicks is associated with a larger percentage of lymphocytes and with higher levels of expression of TLR4 and IL-8 at homeostasis in the three cell subpopulations, as well as with a higher level of expression of LITAF in lymphocytes during the carrier state. In contrast to the early phase of infection, the carrier state is characterized by no major cell recruitment differences between infected and noninfected animals and no significant modification in terms of TLR4, IL-1 beta, IL-8, IL-12, and LITAF expression in all cell subpopulations measured. However, TLR4 expression increased in the lymphocytes of chicks from the susceptible line, reaching the same level as that in infected chicks from the resistant line. These observations suggest that the carrier state is characterized by a lack of immune activation and highlight the interest of working at the level of the cell population rather than that of the organ.