Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity
Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity
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DOI：
10.1172/jci44845
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发表时间：
2011-01-01
影响因子：
15.9
通讯作者：
Umetsu, Dale T.
中科院分区：
文献类型：
--
作者：
Chang, Ya-Jen;Kim, Hye Young;Umetsu, Dale T.
甲型流感病毒的感染代表了世界范围内的主要公共卫生威胁，特别是在患有哮喘的患者中。然而，由甲型流感病毒诱导的免疫可能具有有益的效果，特别是在幼儿中，其可能防止哮喘的后期发展，如卫生假说所建议的。我们发现，用甲型流感病毒感染乳鼠可以保护成年小鼠免受过敏原诱导的气道高反应性（AHR），哮喘的主要特征保护作用与CD 4（-）CD 8（-），而不是CD 4（+），NKT细胞的优先扩增有关，并且需要T-bet和TLR 7将该细胞群连续转移到过敏原致敏的成年小鼠中抑制过敏原诱导的AHR的发展，与过敏原特异性叉头盒p3（+）（Foxp 3（+））Treg细胞群扩增相关的效应通过用来源于幽门螺杆菌的糖脂处理乳鼠来模拟流感诱导的保护作用（一种与预防哮喘有关的细菌）这些发现表明我们认为是一种新的途径，可以调节AHR，以及哮喘的新治疗策略（用NKT细胞群的糖脂激活剂治疗
Infection with influenza A virus represents a major public health threat worldwide, particularly m patients with asthma However, immunity induced by influenza A virus may have beneficial effects, particularly in young children, that might protect against the later development of asthma, as suggested by the hygiene hypothesis Herein, we show that infection of suckling mice with influenza A virus protected the mice as adults against allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma The protective effect was associated with the preferential expansion of CD4(-)CD8(-), but not CD4(+), NKT cells and required T-bet and TLR7 Adoptive transfer of this ell population into allergen-sensitized adult mice suppressed the development of allergen-induced AHR, an effect associated with expansion of the allergen-specific forkhead box p3(+) (Foxp3(+)) Treg cell population Influenza-induced protection was mimicked by treating suckling mice with a glycolipid derived from Helicobacter pylon (a bacterium associated with protection against asthma) that activated NKT cells in a CD1d restricted fashion These findings suggest what we believe to be a novel pathway that can regulate AHR, and a new therapeutic strategy (treatment with glycolipid activators of this NKT cell population) for asthma