EXPRESSION OF THE NATURAL-RESISTANCE GENE LSH IN RESIDENT LIVER MACROPHAGES

EXPRESSION OF THE NATURAL-RESISTANCE GENE LSH IN RESIDENT LIVER MACROPHAGES
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DOI:
10.1128/iai.43.3.1033-1040.1984
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发表时间:
1984-01-01
影响因子:
3.1
通讯作者:
BRADLEY, DJ
BRADLEY, DJ
中科院分区:
医学2区
文献类型:
--
作者:
CROCKER, PR;BLACKWELL, JM;BRADLEY, DJ

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小鼠对多诺瓦利什曼原虫感染的先天抗性和易感性由一个单基因(Lsh)控制,该基因被认为与分别控制鼠伤寒沙门菌和牛分枝杆菌感染早期反应的Ity和Bcg基因相同。揭示了Lsh基因活性的三个新方面。肝巨噬细胞从体内感染的小鼠体内提取后,在体外继续表达Lsh基因活性,尽管在感染2天后才表达耐药表型。对寄生虫早期生长和3h -胸腺嘧啶标记的详细检查表明,这种抗性表型表达的延迟也发生在体内。耐药的表达不受致死照射的影响,但可以通过适当剂量的鼠伤寒沙门氏菌脂多糖或多诺瓦菌膜选择性地增强。显然,耐药机制可能是由常驻肝巨噬细胞与寄生虫源物质相互作用后表达的。这些发现与其他巨噬细胞内病原体的相关性进行了讨论。
Innate resistance and susceptibility to Leishmania donovani infection in mice is controlled by a single gene (Lsh) thought to be identical to the genes Ity and Bcg which control the early response to Salmonella typhimurium and Mycobacterium bovis infections, respectively. Three new aspects of Lsh gene activity were demonstrated. Liver macrophages continue to express Lsh gene activity in vitro after their extraction from mice infected in vivo, although 2 days of infection were required before the resistant phenotype was expressed. Detailed examination of early growth of the parasite and 3H-thymidine labeling of the parasites indicated that this delay in expression of the resistant phenotype also occurred in vivo. The expression of resistance was unaltered by the effects of lethal irradiation but could be selectively enhanced by prior treatment with suitable doses of S. typhimurium lipopolysaccharide or L. donovani membranes. Apparently, the resistance mechanism may be expressed by resident liver macrophages after their interaction with parasite-derived material. The relevance of these findings to the other intramacrophage pathogens is discussed.