Salmonella typhimurium persists within macrophages in the mesenteric lymph nodes of chronically infected Nramp1+/+ mice and can be reactivated by IFNgamma neutralization.

Salmonella typhimurium persists within macrophages in the mesenteric lymph nodes of chronically infected Nramp1+/+ mice and can be reactivated by IFNgamma neutralization.
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鼠伤寒沙门氏菌持续存在于慢性感染 Nramp1+/+ 小鼠肠系膜淋巴结的巨噬细胞内,并可通过 IFNγ 中和重新激活。

DOI:
10.1084/jem.20031319
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发表时间:
2004-01-19
影响因子:
15.3
通讯作者:
Falkow, S
Falkow, S
中科院分区:
医学1区
文献类型:
--
作者:
Monack, DM;Bouley, DM;Falkow, S

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沙门氏菌的宿主适应菌株能够在其宿主中建立持续感染,通常在没有临床疾病的情况下。沙门氏菌感染的小鼠模型主要用作急性全身性疾病的模型。因此,长期S.鼠伤寒沙门氏菌在小鼠中的持久性尚不清楚,也不清楚持续感染的机制。在这里,我们表明,S。尽管存在高水平的抗-S,但鼠伤寒杆菌可在129 sv Nramp 1 + / +(Slc 11 a1 + / +)小鼠的肠系膜淋巴结(MLN)中持续长达1年。鼠伤寒抗体129 sv小鼠定植60 d后的组织中含有大量的炎性病灶和病变,其特征类似于S。伤寒肉芽肿感染365天的小鼠组织几乎没有组织化的炎性病变,但细菌继续存在于MLN中的巨噬细胞内,并且动物通常保持无病。最后,用干扰素-γ中和抗体治疗的慢性感染小鼠表现出急性全身感染的症状,有证据表明大多数组织中细菌复制水平高,粪便脱落水平高。因此,干扰素-γ可能影响巨噬细胞活化水平,在控制持续性S.鼠伤寒杆菌感染。
Host-adapted strains of Salmonella are capable of establishing a persistent infection in their host often in the absence of clinical disease. The mouse model of Salmonella infection has primarily been used as a model for the acute systemic disease. Therefore, the sites of long-term S. typhimurium persistence in the mouse are not known nor are the mechanisms of persistent infection clearly understood. Here, we show that S. typhimurium can persist for as long as 1 yr in the mesenteric lymph nodes (MLNs) of 129sv Nramp1 + / + (Slc11a1 + / +) mice despite the presence of high levels of anti–S. typhimurium antibody. Tissues from 129sv mice colonized for 60 d contain numerous inflammatory foci and lesions with features resembling S. typhi granulomas. Tissues from mice infected for 365 d have very few organized inflammatory lesions, but the bacteria continue to persist within macrophages in the MLN and the animals generally remain disease-free. Finally, chronically infected mice treated with an interferon-γ neutralizing antibody exhibited symptoms of acute systemic infection, with evidence of high levels of bacterial replication in most tissues and high levels of fecal shedding. Thus, interferon-γ, which may affect the level of macrophage activation, plays an essential role in the control of the persistent S. typhimurium infection in mice.
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