Influenza Virus Infects and Depletes Activated Adaptive Immune Responders.
Influenza Virus Infects and Depletes Activated Adaptive Immune Responders.
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DOI：
10.1002/advs.202100693
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Sambhara S
中科院分区：
文献类型：
--
作者：
Bohannon CD;Ende Z;Cao W;Mboko WP;Ranjan P;Kumar A;Mishina M;Amoah S;Gangappa S;Mittal SK;Lovell JF;García-Sastre A;Pfeifer BA;Davidson BA;Knight P;Sambhara S
流感感染在全球范围内导致数百万例严重呼吸道疾病、住院和数十万人死亡。继发性感染是流感高发病率和死亡率的主要原因，并在1918年，1968年和2009年大流行的严重程度中发挥了重要作用。此外，在流感季节，即使在接种疫苗的个体中，其他呼吸道感染的发病率也会增加。对流感季节期间流感疫苗以及其他呼吸道感染疫苗失效的假定机制进行了研究。使用来自流感疫苗接种个体的外周血单核细胞（PBMC）评估对流感、麻疹和水痘的抗原特异性应答。在人类和小鼠模型中进行的观察证实并扩展了该机制。流感病毒感染抑制了针对流感以及其他呼吸道病原体的疫苗接种的持续适应性应答，即，腺病毒和肺炎链球菌通过优先感染和杀死表达高水平唾液酸受体的活化淋巴细胞。这些发现提出了一种新的机制，即由于细菌和其他病毒引起的继发性呼吸道感染的高发病率，以及流感和其他呼吸道病原体的疫苗失效，即使在免疫个体中也是由于流感病毒感染。流感病毒优先靶向激活的适应性免疫应答者，可能是通过增加免疫细胞表面上的唾液酸表达，这允许更多的病毒进入和细胞死亡。这种靶向降低了对流感以及其他呼吸道病原体的免疫应答，并可能导致疫苗效力降低和合并感染增加。
Influenza infections cause several million cases of severe respiratory illness, hospitalizations, and hundreds of thousands of deaths globally. Secondary infections are a leading cause of influenza's high morbidity and mortality, and significantly factored into the severity of the 1918, 1968, and 2009 pandemics. Furthermore, there is an increased incidence of other respiratory infections even in vaccinated individuals during influenza season. Putative mechanisms responsible for vaccine failures against influenza as well as other respiratory infections during influenza season are investigated. Peripheral blood mononuclear cells (PBMCs) are used from influenza vaccinated individuals to assess antigen‐specific responses to influenza, measles, and varicella. The observations made in humans to a mouse model to unravel the mechanism is confirmed and extended. Infection with influenza virus suppresses an ongoing adaptive response to vaccination against influenza as well as other respiratory pathogens, i.e., Adenovirus and Streptococcus pneumoniae by preferentially infecting and killing activated lymphocytes which express elevated levels of sialic acid receptors. These findings propose a new mechanism for the high incidence of secondary respiratory infections due to bacteria and other viruses as well as vaccine failures to influenza and other respiratory pathogens even in immune individuals due to influenza viral infections. Influenza virus preferentially targets activated adaptive immune responders, likely through increased sialic acid expression on immune cell surfaces which allows for greater viral entry and cell death. This targeting reduces immune responders to influenza as well as other respiratory pathogens and can lead to decreased vaccine efficacy and increased co‐infection.
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影响因子：
38.3
作者：
Huang WC;Deng B;Lin C;Carter KA;Geng J;Razi A;He X;Chitgupi U;Federizon J;Sun B;Long CA;Ortega J;Dutta S;King CR;Miura K;Lee SM;Lovell JF
通讯作者：
Lovell JF
DOI：
10.2147/dddt.s70993
发表时间：
2015
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Hraiech S;Papazian L;Rolain JM;Bregeon F
通讯作者：
Bregeon F
影响因子：
15.9
作者：
ABRAMSON, JS;LEWIS, JC;BASS, DA
通讯作者：
BASS, DA
影响因子：
1.3
作者：
Holka, Justyna;Pawlak, Katarzyna;Ciepiela, Olga
通讯作者：
Ciepiela, Olga
影响因子：
3.1
作者：
BROWNSON, JM;MAHY, BWJ;HAZLEMAN, BL
通讯作者：
HAZLEMAN, BL