Chen Hong D, Fraire Armando E, Joris Isabelle, Welsh Raymond M, Selin Liisa K
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Am J Pathol. 2003 Oct;163(4):1341-55. doi: 10.1016/S0002-9440(10)63493-1.
Having previously shown that previous immunity to one virus can influence the host response to a subsequent unrelated virus, we questioned whether the outcome to a given virus infection would be altered in similar or different ways by previous immunity to different viruses, and whether immunity to a given virus would have similar effects on all subsequent infections. In mouse models of respiratory viral infections, immunity to lymphocytic choriomeningitis virus (LCMV), murine cytomegalovirus (MCMV), or influenza A virus enhanced both Th1-type cytokine responses and viral clearance in the lung on vaccinia virus infection. A common pathological feature was the presence of chronic mononuclear infiltrates instead of the acute polymorphonuclear response seen in the infected nonimmune mice, but some pathologies such as enhanced bronchus-associated lymphoid tissue and bronchiolitis obliterans were unique for the immunizing virus, LCMV. Immunity to influenza virus influenced subsequent infections diversely, inhibiting vaccinia virus but enhancing LCMV and MCMV titers and completely altering cytokine profiles. Influenza virus immunity enhanced the mild mononuclear responses usually observed during acute infections with MCMV or LCMV in nonimmune mice, but unique features such as enhanced bronchiolization and mononuclear consolidation occurred during MCMV infection of influenza virus-immune mice. Heterologous immunity induced two patterns of disease outcome dependent on the specific virus infection sequence: improved, if the acute response switched from a neutrophilic to a lymphocytic response or worsened, if it switched from a mild to a severe lymphocytic response. Heterologous immunity thus occurs between many viruses, resulting in altered protective immunity and lung immunopathology, and this is influenced by the specific virus infection sequence.
此前我们已经表明，对一种病毒的既往免疫可影响宿主对随后无关病毒的反应，我们由此提出疑问：既往对不同病毒的免疫是否会以相似或不同的方式改变对特定病毒感染的结果，以及对特定病毒的免疫是否会对所有后续感染产生相似的影响。在呼吸道病毒感染的小鼠模型中，对淋巴细胞性脉络丛脑膜炎病毒（LCMV）、鼠巨细胞病毒（MCMV）或甲型流感病毒的免疫增强了接种痘苗病毒时肺部的Th1型细胞因子反应和病毒清除。一个共同的病理特征是存在慢性单核细胞浸润，而非感染的未免疫小鼠中出现的急性多形核细胞反应，但某些病理变化，如支气管相关淋巴组织增强和闭塞性细支气管炎，是免疫接种病毒LCMV所特有的。对流感病毒的免疫对后续感染的影响各不相同，抑制了痘苗病毒，但提高了LCMV和MCMV滴度，并完全改变了细胞因子谱。流感病毒免疫增强了未免疫小鼠在急性感染MCMV或LCMV期间通常观察到的轻度单核细胞反应，但在流感病毒免疫小鼠感染MCMV期间出现了如支气管化生增强和单核细胞实变等独特特征。异源免疫诱导了两种疾病结局模式，这取决于特定的病毒感染顺序：如果急性反应从中性粒细胞反应转变为淋巴细胞反应，则病情改善；如果从轻度淋巴细胞反应转变为重度淋巴细胞反应，则病情恶化。因此，许多病毒之间会发生异源免疫，导致保护性免疫和肺部免疫病理学改变，而这受到特定病毒感染顺序的影响。
