Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection.
Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection.
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DOI：
10.4049/jimmunol.1601896
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发表时间：
2017-05-15
期刊：
影响因子：
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通讯作者：
Perlman S
中科院分区：
文献类型：
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作者：
Channappanavar R;Fett C;Mack M;Ten Eyck PP;Meyerholz DK;Perlman S
致病性人类冠状病毒，如严重急性呼吸综合征冠状病毒（SARS-CoV）和中东呼吸综合征冠状病毒（MERS-CoV），会导致急性呼吸道疾病。2002-2003年SARS流行和最近MERS的流行病学数据表明，疾病结局可能存在性别依赖性差异。为了研究这些差异，我们用SARS-CoV感染了不同年龄组的雄性和雌性小鼠，并分析了它们对感染的易感性。我们的研究结果表明，与年龄匹配的雌性小鼠相比，雄性小鼠对SARS-CoV感染更敏感。对SARS-CoV感染的性别偏见程度随着年龄的增长而增加，中年小鼠与年轻小鼠相比表现出更明显的差异。雄性小鼠对SARS-CoV的易感性增强与病毒滴度升高、血管渗漏增强和肺泡水肿有关。这些变化伴随着雄性小鼠肺中炎性单核巨噬细胞（IMM）和中性粒细胞的积累增加，IMM的消耗部分保护这些小鼠免受致命的SARS。此外，性别特异性差异是独立的T和B细胞反应。此外，卵巢切除术或雌激素受体拮抗剂治疗雌性小鼠的死亡率增加，表明雌激素受体信号在感染SARS冠状病毒的小鼠中具有保护作用。总之，这些数据表明，小鼠对SARS-CoV易感性的性别差异与在患者中观察到的相似，并且还确定雌激素受体信号传导对女性的保护至关重要。
Pathogenic human coronaviruses such as the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) cause acute respiratory illness. Epidemiological data from the 2002-2003 SARS epidemic and recent MERS indicate that there may be sex-dependent differences in disease outcomes. To investigate these differences, we infected male and female mice of different age groups with SARS-CoV and analyzed their susceptibility to the infection. Our results showed that male mice were more susceptible to SARS-CoV infection compared to age matched females. The degree of sex-bias to SARS-CoV infection increased with advancing age such that middle-aged mice showed much more pronounced differences compared to young mice. Enhanced susceptibility of male mice to SARS-CoV was associated with elevated virus titers, enhanced vascular leakage and alveolar edema. These changes were accompanied by increased accumulation of inflammatory monocyte macrophages (IMMs) and neutrophils in the lungs of male mice and depletion of IMMs partially protected these mice from lethal SARS. Moreover, the sex-specific differences were independent of T and B cell responses. Furthermore, ovariectomy or treating female mice with an estrogen receptor antagonist increased mortality indicating a protective effect for estrogen receptor signaling in mice infected with SARS-CoV. Together, these data suggest that sex differences in susceptibility to SARS-CoV in mice parallel those observed in patients and also identify estrogen receptor signaling as critical for protection in females.