Immune Responses in Oral Papillomavirus Clearance in the MmuPV1 Mouse Model.

Immune Responses in Oral Papillomavirus Clearance in the MmuPV1 Mouse Model.
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MmuPV1小鼠模型中口腔乳头瘤病毒清除的免疫应答。

DOI:
10.3390/pathogens12121452
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发表时间:
2023-12-14
期刊:
Pathogens (Basel, Switzerland)
影响因子:
--
通讯作者:
Hu J
Hu J
中科院分区:
其他
文献类型:
--
作者:
Brendle SA;Li JJ;Walter V;Schell TD;Kozak M;Balogh KK;Lu S;Christensen ND;Zhu Y;El-Bayoumy K;Hu J

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人乳头瘤病毒(HPV)诱导的口咽癌现已超过HPV诱导的宫颈癌,并存在明显的性别偏见。虽然已经确定女性具有更熟练的免疫系统,但仍不清楚口腔乳头状瘤病毒感染的免疫控制是否在性别之间存在差异。在目前的研究中,我们使用转基因小鼠靶向CCR 2和Stat 1途径,目的是研究先天性和适应性免疫反应在清除口腔乳头瘤病毒中的作用,使用我们建立的乳头瘤病毒(MmuPV 1)感染模型。在T和B细胞缺陷的Rag 1 ko小鼠中检测到持续性口服MmuPV 1感染。与此同时,其他受试小鼠对MmuPV 1感染易感,但能够清除病毒。我们在野生型和Stat 1 ko小鼠感染的舌头中发现了关键骨髓细胞(包括巨噬细胞、中性粒细胞和树突状细胞)的性别差异,但在CCR 2ko小鼠中未观察到这些差异。有趣的是,我们还观察到抗MmuPV 1 E4抗体水平的性别差异,特别是对于两种IgG同种型:IgG 2b和IgG 3。然而,我们发现相当数量的干扰素-γ产生的CD 8 T细胞刺激E6和E7在两种性别。这些发现表明,男性和女性可能使用不同的先天性和适应性免疫反应的组成部分,以控制乳头瘤病毒感染的MmuPV 1小鼠模型。观察到的免疫反应的性别差异,特别是在骨髓细胞,包括树突状细胞(DC)亚群,可能有潜在的诊断和预后价值HPV相关的口咽癌。
Human papillomavirus (HPV)-induced oropharyngeal cancer now exceeds HPV-induced cervical cancer, with a noticeable sex bias. Although it is well established that women have a more proficient immune system, it remains unclear whether immune control of oral papillomavirus infections differs between sexes. In the current study, we use genetically modified mice to target CCR2 and Stat1 pathways, with the aim of investigating the role of both innate and adaptive immune responses in clearing oral papillomavirus, using our established papillomavirus (MmuPV1) infection model. Persistent oral MmuPV1 infection was detected in Rag1ko mice with T and B cell deficiencies. Meanwhile, other tested mice were susceptible to MmuPV1 infections but were able to clear the virus. We found sex differences in key myeloid cells, including macrophages, neutrophils, and dendritic cells in the infected tongues of wild type and Stat1ko mice but these differences were not observed in CCR2ko mice. Intriguingly, we also observed a sex difference in anti-MmuPV1 E4 antibody levels, especially for two IgG isotypes: IgG2b and IgG3. However, we found comparable numbers of interferon-gamma-producing CD8 T cells stimulated by E6 and E7 in both sexes. These findings suggest that males and females may use different components of innate and adaptive immune responses to control papillomavirus infections in the MmuPV1 mouse model. The observed sex difference in immune responses, especially in myeloid cells including dendritic cell (DC) subsets, may have potential diagnostic and prognostic values for HPV-associated oropharyngeal cancer.
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