IL-10 Underlies Distinct Susceptibility of BALB/c and C57BL/6 Mice to Mycobacterium avium Infection and Influences Efficacy of Antibiotic Therapy1
IL-10 Underlies Distinct Susceptibility of BALB/c and C57BL/6 Mice to Mycobacterium avium Infection and Influences Efficacy of Antibiotic Therapy1
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IL-10 是 BALB/c 和 C57BL/6 小鼠对鸟分枝杆菌感染的不同敏感性的基础，并影响抗生素治疗的疗效1
作者：
Susana Roque;C. Nobrega;R. Appelberg;M. Correia
IL-10 产生的增加常常与感染的易感性增加有关。然而，IL-10活性与分枝杆菌感染易感性之间的相关性仍不确定。尽管使用过度表达 IL-10 的转基因小鼠进行的研究一致表明对分枝杆菌感染的易感性增加，但降低或消除 IL-10 活性的实验方法却得出了不确定的数据。我们在这里表明，这种争议可能是由于各种实验过程中使用的小鼠品系造成的。我们的结果表明，BALB/c 小鼠比 C57BL/6 小鼠更容易受到鸟分枝杆菌感染。 BALB/c 小鼠的易感性增加在很大程度上是由于两种小鼠品系之间 IL-10 的不同活性所致。相应地，通过施用抗IL-10R mAb降低IL-10活性，或在IL-10敲除小鼠中研究的不存在IL-10，明显降低了BALB/c小鼠对鸟分枝杆菌的易感性，但在C57BL/6小鼠中效果不太明显。此外，在受感染的 BALB/c 小鼠中消除 IL-10 活性会增加抗分枝杆菌治疗的功效，而对于 C57BL/6 小鼠则没有效果。这些观察结果表明，IL-10 对相同分枝杆菌刺激的反应活性不仅影响感染的易感性，而且影响抗分枝杆菌治疗的功效。现在应该在人类对分枝杆菌感染的反应的背景下考虑这一点，特别是作为改善分枝杆菌感染治疗的可能策略。
Increased production of IL-10 has been frequently associated with augmented susceptibility to infection. However, the correlation between IL-10 activity and susceptibility to mycobacterial infection is still uncertain. Although studies using transgenic mice overexpressing IL-10 consistently showed an increased susceptibility to mycobacterial infection, experimental approaches in which IL-10 activity was reduced or abrogated originated inconclusive data. We show here that this controversy might be due to the mouse strains used in the various experimental procedures. Our results show that BALB/c mice are more susceptible than C57BL/6 to Mycobacterium avium infection. This increased susceptibility of BALB/c mice is, to a great extent, due to distinct activity of IL-10 between the two mouse strains. In accordance, reduction of IL-10 activity through the administration of anti-IL-10R mAb, or the absence of IL-10 as studied in IL-10 knockout mice, clearly decreased the susceptibility of BALB/c mice to M. avium but had a less obvious effect in C57BL/6 mice. Moreover, abrogation of IL-10 activity in infected BALB/c mice increased the efficacy of antimycobacterial therapy, whereas for the C57BL/6 mice it produced no effect. These observations show that the activity of IL-10 in response to the same mycobacterial stimulus influences not only the susceptibility to infection but also the efficacy of antimycobacterial therapy. This should now be considered in the context of human response to mycobacterial infection, particularly as a possible strategy to improve treatment against infections by mycobacteria.
影响因子：
15.9
作者：
Boussiotis, VA;Tsai, EY;Goldfeld, AE
通讯作者：
Goldfeld, AE
影响因子：
4.4
作者：
M. Greenberger;R. Strieter;S. Kunkel;J. Danforth;R. Goodman;T. Standiford
通讯作者：
M. Greenberger;R. Strieter;S. Kunkel;J. Danforth;R. Goodman;T. Standiford