Murine Q Fever Vaccination Model Reveals Sex Dimorphism in Early Phase Delayed-Type Hypersensitivity Responses.
Murine Q Fever Vaccination Model Reveals Sex Dimorphism in Early Phase Delayed-Type Hypersensitivity Responses.
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DOI：
10.3389/fimmu.2022.894536
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发表时间：
2022
影响因子：
7.3
通讯作者：
Long, Carrie Mae
中科院分区：
文献类型：
--
作者：
Binette, Picabo;Tesfamariam, Mahelat;Cockrell, Diane;Heinzen, Robert A.;Richards, Crystal;Shaia, Carl;Long, Carrie Mae
关键词：
对微生物疫苗和相关组分的迟发型超敏反应（DTH）是广泛许可全细胞疫苗（如Q热疫苗）的主要障碍。Q热是一种由胞内细菌贝氏柯克斯体引起的人畜共患疾病。目前唯一获得许可的疫苗Q-Vax®是一种全细胞灭活制剂，与先前致敏个体接种疫苗后可能发生的严重皮肤DTH反应相关。为了研究这种反应的潜在免疫学机制并更好地代表在人类中观察到的早期DTH反应，开发并采用了鼠致敏和皮肤试验模型。雌性C57 Bl/6 J小鼠在致敏和激发后表现出最稳健的早期DTH反应，与它们的雄性对应物和其他小鼠品系相比。在用Q fever全细胞疫苗致敏和激发后，测量了皮肤、引流淋巴结和血清中的免疫反应。真皮中的局部免疫应答的特征在于主要涉及中性粒细胞、巨噬细胞和T细胞的炎症。次级淋巴器官分析显示不同的免疫学特征后，敏化和诱导与性别为基础的二分法的T细胞表型和抗原呈递细胞数量。除了提供一个Q热疫苗接种后的DTH模型，概括早期DTH事件，这些数据表明，性别是一个主要因素影响的幅度和随后的反应的组成。
Delayed-type hypersensitivity (DTH) responses to microbial vaccines and related components are a major roadblock for widespread licensing of whole cell vaccines such as that of Q fever. Q fever is a zoonotic disease caused by the intracellular bacterium Coxiella burnetii. The only currently licensed vaccine, Q-Vax®, is a whole cell inactivated formulation that is associated with a potentially severe dermal post vaccination DTH response in previously sensitized individuals. To investigate the underlying immunologic mechanisms of this response and better represent the early-phase DTH response observed in humans, a murine sensitization and skin testing model was developed and employed. Female C57Bl/6J mice displayed the most robust early-phase DTH responses following sensitization and elicitation compared to their male counterparts and other mouse strains. Immunologic responses were measured within the skin, draining lymph nodes, and serum following both sensitization and elicitation with Q fever whole cell vaccines. Local immunologic responses in the dermis were characterized by inflammation primarily involving neutrophils, macrophages, and T cells. Secondary lymphoid organ profiling revealed distinct immunological signatures following both sensitization and elicitation with a sex-based dichotomy in T cell phenotypes and antigen presenting cell numbers. Beyond providing a post-Q fever vaccination DTH model that recapitulates early-phase DTH events, these data suggest that sex is a primary factor influencing the magnitude and composition of the ensuing response.
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影响因子：
--
作者：
Kashem, Sakeen W;Kaplan, Daniel H
通讯作者：
Kaplan, Daniel H
影响因子：
3.7
作者：
Keijmel SP;Delsing CE;Sprong T;Bleijenberg G;van der Meer JW;Knoop H;Bleeker-Rovers CP
通讯作者：
Bleeker-Rovers CP
影响因子：
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作者：
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通讯作者：
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影响因子：
3.1
作者：
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通讯作者：
BERMAN, MA
影响因子：
2.5
作者：
Kobayashi, K;Kaneda, K;Kasama, T
通讯作者：
Kasama, T