Mucosal immunity to influenza without IgA: an IgA knockout mouse model.
Mucosal immunity to influenza without IgA: an IgA knockout mouse model.
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DOI：
10.4049/jimmunol.162.5.2530
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发表时间：
1999-03
影响因子：
4.4
通讯作者：
I. Mbawuike;S. Pacheco;C. Acuna;Kirsten Switzer;Yongxin Zhang;G. Harriman
中科院分区：
文献类型：
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作者：
I. Mbawuike;S. Pacheco;C. Acuna;Kirsten Switzer;Yongxin Zhang;G. Harriman
通过基因靶向产生伊加敲除小鼠（伊加-/-），并用于确定伊加在保护粘膜免受流感感染中的作用以及免疫对优先诱导分泌伊加的价值。用亚致死和致死剂量的流感病毒对幼稚伊加-/-小鼠及其野生型伊加+/+同窝小鼠进行气溶胶攻击，导致肺部病毒感染和死亡率水平相似。流感疫苗加霍乱毒素/霍乱毒素B的鼻内和腹膜内免疫在伊加+/+（但不是伊加-/-）小鼠中诱导显著的粘膜和血清流感血凝素特异性伊加Ab，以及在伊加-/-和伊加+/+小鼠中诱导显著的IgG和IgM Ab;在致死性流感病毒攻击后，两者均表现出相似水平的肺部和鼻腔病毒复制和死亡率。单克隆抗血凝素IgG 1、IgG 2a、IgM和多聚伊加抗体在预防伊加-/-小鼠流感病毒感染方面同样有效。这些结果表明，伊加不是预防流感病毒感染和疾病所必需的。实际上，虽然用于选择性诱导伊加对抗流感的粘膜免疫可构成用于控制流感和其它呼吸道病毒感染的有用方法，但另外刺激其它Ig的策略可能更合乎需要。
IgA knockout mice (IgA-/-) were generated by gene targeting and were used to determine the role of IgA in protection against mucosal infection by influenza and the value of immunization for preferential induction of secretory IgA. Aerosol challenge of naive IgA-/- mice and their wild-type IgA+/+ littermates with sublethal and lethal doses of influenza virus resulted in similar levels of pulmonary virus infection and mortality. Intranasal and i.p. immunization with influenza vaccine plus cholera toxin/cholera toxin B induced significant mucosal and serum influenza hemagglutinin-specific IgA Abs in IgA+/+ (but not IgA-/-) mice as well as IgG and IgM Abs in both IgA-/- and IgA+/+ mice; both exhibited similar levels of pulmonary and nasal virus replication and mortality following a lethal influenza virus challenge. Monoclonal anti-hemagglutinin IgG1, IgG2a, IgM, and polymeric IgA Abs were equally effective in preventing influenza virus infection in IgA-/- mice. These results indicate that IgA is not required for prevention of influenza virus infection and disease. Indeed, while mucosal immunization for selective induction of IgA against influenza may constitute a useful approach for control of influenza and other respiratory viral infections, strategies that stimulate other Igs in addition may be more desirable.