Contribution of IL-1 to resistance to Streptococcus pneumoniae infection

Contribution of IL-1 to resistance to Streptococcus pneumoniae infection
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DOI:
10.1093/intimm/dxn071
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发表时间:
2008-09-01
影响因子:
4.4
通讯作者:
Mizrachi-Nebenzahl, Yaffa
Mizrachi-Nebenzahl, Yaffa
中科院分区:
医学3区
文献类型:
--
作者:
Kafka, Daniel;Ling, Eduard;Mizrachi-Nebenzahl, Yaffa

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在鼻内接种后,在IL-1家族基因缺陷小鼠[即IL-1 α(-/-)、IL-1 β(-/-)、IL-1 α/β(-/-)和IL-1 R拮抗剂(IL-1 Ra)(-/-)小鼠]中研究了IL-1在肺炎链球菌感染易感性中的作用。鼻内接种S.与对照、IL-1 α(-/-)和IL-1 Ra(-/-)小鼠相比,IL-1 β(-/-)和IL-1 α/β(-/-)小鼠的肺炎链球菌感染显示出显著较低的存活率和较高的鼻咽和肺细菌负荷。用rIL-1 β治疗IL-1 β(-/-)小鼠显著改善了它们的存活率。在对照组、IL-1 α(-/-)和IL-1 R α(-/-)小鼠中发现血液中性粒细胞显著增加,但在IL-1 β(-/-)和IL-1 α/β(-/-)小鼠中未发现。在IL-1 α(-/-)和对照小鼠的肺中观察到中性粒细胞的局部浸润和相对保存的器官结构。然而,S.肺炎感染的IL-1 β(-/-)、IL-1 α/β(-/-)和IL-1 Ra(-/-)小鼠表现出弥漫性肺炎和组织损伤。总之,所有三种亚型都有助于保护免受S。我们的结果指出IL-1 α和IL-1 β在肺炎链球菌的发病机制和控制中的不同作用。pneumoniae感染,表明IL-1 β在抵抗原发性肺炎球菌感染中起主要作用,而IL-1 α的作用不太重要。
The role of IL-1 in susceptibility to Streptococcus pneumoniae infection was studied in mice deficient in genes of the IL-1 family [i.e. IL-1 alpha(-/-), IL-1 beta(-/-), IL-1 alpha/beta(-/-) and IL-1R antagonist (IL-1Ra)(-/-) mice] following intra-nasal inoculation. Intra-nasal inoculation of S. pneumoniae of IL-1 beta(-/-) and IL-1 alpha/beta(-/-) mice displayed significantly lower survival rates and higher nasopharyngeal and lung bacterial load as compared with control, IL-1 alpha(-/-) and IL-1Ra(-/-) mice. Treatment of IL-1 beta(-/-) mice with rIL-1 beta significantly improved their survival. A significant increase in blood neutrophils was found in control, IL-1 alpha(-/-) and IL-1R alpha(-/-) but not in IL-1 beta(-/-) and IL-1 alpha/beta(-/-) mice. Local infiltrates of neutrophils and relatively preserved organ architecture were observed in the lungs of IL-1 alpha(-/-) and control mice. However, S. pneumoniae-infected IL-1 beta(-/-), IL-1 alpha/beta(-/-) and IL-1Ra(-/-) mice demonstrated diffuse pneumonia and tissue damage. Altogether, all three isoforms contribute to protection against S. pneumoniae; our results point to differential role of IL-1 alpha and IL-1 P in the pathogenesis and control of S. pneumoniae infection and suggest that IL-1 beta has a major role in resistance to primary pneumococcal infection while the role of IL-1 alpha is less important.