Mucosal Immunology最新文献_第5页

Corrigendum “RIPK3 and Caspase-8 interpret cytokine signals to regulate ILC3 survival in the gut”. [Mucosal Immunol. 17/6 (2024) 1212–1221] 更正“RIPK3和Caspase-8解释细胞因子信号以调节肠道中ILC3的存活”。[j].中华口腔医学杂志，2016,32(2):1212-1221。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Mucosal Immunology

Pub Date : 2025-12-01 DOI: 10.1016/j.mucimm.2025.11.002

Ann M. Joseph , Anees Ahmed , Jeremy Goc , Veronika Horn , Brooke Fiedler , Dario Garone , John B. Grigg , Jazib Uddin , Fei Teng , Melanie Fritsch , Eric Vivier , Gregory F. Sonnenberg

引用次数: 0

T-cell immunity against influenza virus does not require Th1 or Th17 master regulator transcription factors t细胞对流感病毒的免疫不需要Th1或Th17主调节转录因子。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Mucosal Immunology

Pub Date : 2025-12-01 DOI: 10.1016/j.mucimm.2025.08.005

Kunal Dhume , Caroline M. Finn , Eugene Baffoe , Lauren A. Kimball , Siva N. Annamalai , Verónica Urdaneta-Páez , Jash Trivedi , Taj Azarian , Tara M. Strutt , K. Kai McKinstry

Transcriptional programming needed for CD4 T cell immunity against influenza A virus (IAV) is unclear. Most antiviral CD4 T cells fit Th1 criteria, but cells unable to develop Th1 identity, through deletion of the transcription factors T-bet and Eomesodermin, remain protective. These double knockout (DKO) cells produce Th17 cytokines and express the Th17 ‘master regulator’, Rorγt, supporting the concept that Th17 programming is needed for Th1-independent T cell immunity. Here, we directly tested requirements for Rorγt in promoting this mode of protection using T-bet/Eomesodermin/Rorγt triple knockout (TKO) mice. We show that Th17 functions are dramatically reduced in TKO cells but that they can nevertheless transfer protection against IAV to unprimed wildtype mice. Furthermore, TKO mice efficiently clear primary IAV infection, resist lethal bacterial superinfection, and generate antibody-dependent immunity against reinfection with the same virus. Finally, T cell-dependent heterosubtypic immunity is similarly effective in IAV-primed TKO, DKO, and wildtype mice. However, strikingly different T cell response patterns and inflammatory landscapes underlie these protective outcomes, highlighted in TKO mice by Th2-linked components not typically associated with efficient viral clearance. Our results reveal an unexpected degree of flexibility in T cell responses able to combat IAV, underscoring their potential to enhance vaccine strategies.

CD4 T细胞免疫甲型流感病毒（IAV）所需的转录编程尚不清楚。大多数抗病毒CD4 T细胞符合Th1标准，但无法形成Th1身份的细胞，通过删除转录因子T-bet和Eomesodermin，仍然具有保护作用。这些双敲除（DKO）细胞产生Th17细胞因子并表达Th17“主调节因子”Rorγt，支持Th17编程是th1非依赖性T细胞免疫所必需的概念。在这里，我们使用T-bet/Eomesodermin/Rorγt三敲除（TKO）小鼠直接测试了Rorγt在促进这种保护模式中的需求。我们发现Th17的功能在TKO细胞中显著降低，但它们仍然可以将抗IAV的保护转移到未引物的野生型小鼠身上。此外，TKO小鼠可以有效清除原发性IAV感染，抵抗致命的细菌重复感染，并对同一病毒的再感染产生抗体依赖免疫。最后，T细胞依赖性异亚型免疫在iav启动的TKO、DKO和野生型小鼠中同样有效。然而，显著不同的T细胞反应模式和炎症景观是这些保护性结果的基础，在TKO小鼠中，th2相关成分通常与有效的病毒清除无关。我们的研究结果揭示了能够对抗IAV的T细胞反应具有意想不到的灵活性，强调了它们增强疫苗策略的潜力。

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引用次数: 0

Clostridioides difficile toxin A and toxin B inhibit toxin-specific adaptive immune responses through glucosyltransferase-dependent activity 艰难梭菌毒素A和毒素B通过糖基转移酶依赖活性抑制毒素特异性适应性免疫反应。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Mucosal Immunology

Pub Date : 2025-12-01 DOI: 10.1016/j.mucimm.2025.08.004

Jeffrey R. Maslanka , Jennifer A. Londregan , Joshua E. Denny , Ellie N. Hulit , Nontokozo V. Mdluli , F. Christopher Peritore-Galve , Md Zahidul Alam , Mohamad-Gabriel Alameh , D. Borden Lacy , Joseph P. Zackular , Michael C. Abt

Clostridioides difficile colonizes the gastrointestinal tract and secretes two virulence factors: toxin A (TcdA) and toxin B (TcdB). Protective immunity against C. difficile infection is limited as patients are susceptible to multiple rounds of recurrent infections. The factors determining whether immunity to TcdA and TcdB is generated remain incompletely defined. We determined that C. difficile-infected mice generate antibody and IL-17A-producing CD4⁺ T cell responses to TcdA but not TcdB. To determine the mechanism of the failed anti-TcdB immunity, C. difficile mutant strains expressing glucosyltransferase inactive (GTX) TcdA, and/or glucosyltransferase inactive TcdB were used. Infection with TcdB_GTX or dual mutant (TcdA_GTX TcdB_GTX) restored TcdB-specific antibody responses, while infection with TcdA_GTX or TcdA_GTX TcdB_GTX led to an earlier induction of TcdA-specific antibodies. Finally, infection with the dual GTX mutant enhanced TcdA and TcdB-specific CD4⁺ T cell responses. These data demonstrate that the glucosyltransferase activity of TcdA and TcdB hinders the antigen-specific adaptive immune response to itself and may be a mechanism that underlies high recurrence rates following C. difficile infection in patients.

艰难梭菌定植胃肠道，分泌毒素A （TcdA）和毒素B （TcdB）两种毒力因子。由于患者易受多轮反复感染，对艰难梭菌感染的保护性免疫是有限的。决定是否产生对TcdA和TcdB免疫的因素仍然不完全确定。我们确定了艰难梭菌感染的小鼠对TcdA产生抗体和产生il - 17a的CD4+ T细胞反应，而不是TcdB。为了确定抗TcdB免疫失败的机制，使用表达葡萄糖基转移酶失活（GTX） TcdA和/或葡萄糖基转移酶失活TcdB的艰难梭菌突变菌株。感染TcdBGTX或双突变体（TcdAGTX TcdBGTX）可恢复tcddb特异性抗体反应，而感染TcdAGTX或TcdAGTX TcdBGTX可更早诱导tcdda特异性抗体。最后，感染双GTX突变体增强了TcdA和tcdb特异性CD4+ T细胞反应。这些数据表明，TcdA和TcdB的糖基转移酶活性阻碍了抗原特异性适应性免疫应答，这可能是患者在艰难梭菌感染后高复发率的机制。

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引用次数: 0

C10ORF99 (GPR15L) increases susceptibility to colitis and colitis-induced colorectal cancer via GPR15-independent mechanisms, while mediating GPR15-dependent T cell migration to the large intestine C10ORF99 （GPR15L）通过不依赖gpr15的机制增加结肠炎和结肠炎诱导的结直肠癌的易感性，同时介导依赖gpr15的T细胞向大肠迁移。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Mucosal Immunology

Pub Date : 2025-12-01 DOI: 10.1016/j.mucimm.2025.08.001

Gerald J. O’Connor , Rachel M. Wigmore , Nguyen T. Van , Jihae C. Choi , Karen Zhang , Charles Kivolowitz , Alessandra Chen , Manju Ambelil , Dan R. Littman , Sangwon V. Kim

GPR15 is a homing receptor important for T cell migration to the large intestine, the primary site of inflammation in ulcerative colitis. Both GPR15 and its ligand, C10ORF99, represent potential therapeutic targets for the treatment of IBD; however, the roles of C10ORF99 in the large intestine are not fully elucidated. Here, we demonstrate that C10ORF99 is the non-redundant ligand of GPR15 mediating T cell migration to the large intestine. Furthermore, we demonstrate that C10ORF99 has GPR15-independent functions in the large intestine: C10ORF99 deficiency is protective in chemically induced colitis, and this appears to result from enhanced epithelial barrier regeneration. We found that C10ORF99 can inhibit intestinal epithelial proliferation in a cell-intrinsic manner. Additionally, due to this protection from colitis development in the absence of C10ORF99, C10ORF99 KO is also protected from colitis-associated colorectal cancer development. These data indicate that the deficiency of C10ORF99 can not only block pathogenic T cell migration to the large intestine, but can also promote epithelial barrier repair, potentially offering additional advantages for recovery from ulcerative colitis.

GPR15是一种重要的T细胞迁移到大肠的归巢受体，大肠是溃疡性结肠炎炎症的主要部位。GPR15及其配体C10ORF99都是治疗IBD的潜在治疗靶点；然而，C10ORF99在大肠中的作用尚未完全阐明。在这里，我们证明了C10ORF99是介导T细胞迁移到大肠的GPR15的非冗余配体。此外，我们证明C10ORF99在大肠中具有不依赖gpr15的功能：C10ORF99缺乏在化学诱导的结肠炎中具有保护作用，这似乎是由于上皮屏障再生增强所致。我们发现C10ORF99能够以细胞内在的方式抑制肠上皮细胞的增殖。此外，由于在缺乏C10ORF99的情况下对结肠炎发展的保护作用，C10ORF99 KO也可以防止结肠炎相关的结直肠癌发展。这些数据表明，缺乏C10ORF99不仅可以阻止致病性T细胞向大肠迁移，还可以促进上皮屏障修复，可能为溃疡性结肠炎的恢复提供额外的优势。

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引用次数: 0

Neutrophil-chemoattractant CXCL5 increases lung barrier permeability in acute lung injury 中性粒细胞趋化剂CXCL5增加急性肺损伤肺屏障通透性。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Mucosal Immunology

Pub Date : 2025-12-01 DOI: 10.1016/j.mucimm.2025.10.003

Sarah Berger , Cengiz Goekeri , Peter Pennitz , Birgitt Gutbier , Laura Michalick , Karen Hoffmann , Elena Lopez-Rodriguez , Vladimir Gluhovic , Sandra-Maria Wienhold , Ulrike Behrendt , Alexander Taylor , Kristina Dietert , Holger Kirsten , Sandra Kunder , Kristina Mueller , Markus Weigel , Torsten Hain , Sarah M. Volkers , Sebastian Weis , Achim D. Gruber , Geraldine Nouailles

Acute lung injury is a common complication of pneumonia, with disease severity linked to inflammatory cell recruitment and lung barrier dysfunction. In this study, we investigate the role of neutrophil-chemoattractant CXCL5 in lung barrier function and inflammation.

We examined CXCL5 in patients with severe pneumonia and in in vitro and in vivo models of acute lung injury. Pneumococcal infection and mechanical ventilation triggered CXCL5 release in both humans and mice. In Cxcl5-deficient mice, the alveolar-epithelial barrier remained intact despite acute lung injury, independent of alveolar neutrophil recruitment. Single-cell transcriptomics revealed enhanced cell junctional transcripts in epithelial cells of Cxcl5-deficient mice. Consistently, CXCL5 exposure disrupted the barrier function of TNF-primed human primary alveolar epithelial cells.

Beyond its known role in neutrophil recruitment, CXCL5 independently increases alveolar-epithelial barrier permeability. Therefore, targeting CXCL5 inhibition as adjunctive therapy with antibiotics in severe bacterial pneumonia may help reduce excessive inflammation and preserve lung barrier function.

急性肺损伤是肺炎的常见并发症，疾病严重程度与炎症细胞募集和肺屏障功能障碍有关。在这项研究中，我们探讨了中性粒细胞趋化剂CXCL5在肺屏障功能和炎症中的作用。我们在重症肺炎患者和体外和体内急性肺损伤模型中检测了CXCL5。肺炎球菌感染和机械通气触发人类和小鼠的CXCL5释放。在缺乏cxcl5的小鼠中，尽管急性肺损伤，肺泡上皮屏障保持完整，不依赖肺泡中性粒细胞的募集。单细胞转录组学显示，cxcl5缺陷小鼠上皮细胞的细胞连接转录增强。同样，CXCL5暴露破坏了tnf引发的人原代肺泡上皮细胞的屏障功能。除了已知的在中性粒细胞募集中的作用外，CXCL5还能独立增加肺泡上皮屏障的通透性。因此，针对CXCL5抑制作为抗生素治疗重症细菌性肺炎的辅助治疗可能有助于减少过度炎症和保护肺屏障功能。

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引用次数: 0

Expansion of genital Tregs reduces neutrophil influx and maintains mucosal barrier integrity during inflammatory bacteria challenge 生殖器Tregs的扩张减少中性粒细胞内流，并在炎症细菌攻击期间维持粘膜屏障的完整性。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Mucosal Immunology

Pub Date : 2025-12-01 DOI: 10.1016/j.mucimm.2025.08.006

Faisal Nuhu , Marina Costa-Fujishima , Christina Gavino , Aloysious Ssemaganda , Melika Verdipanah , Naima Jahan , Thomas Murooka , Lyle R. McKinnon

Genital inflammation is associated with increased HIV risk. We previously found that endocervical Tregs correlated with decreased genital inflammation and reduced HIV target cells. IL-2 induces Tregs, and efforts to potentiate its regulatory activities clinically are ongoing. In this study, intraperitoneal administration of IL-2 conjugated to IL-2mAb clone JES6-1A12 (IL2C-trimeric) in estrous-synchronized female FoxP3^GFP mice selectively expanded Tregs in the lower female genital tract, with limited effects on non-Treg cells. IL2C-trimeric increased the expression of GITR on Tregs, and most Tregs expressed tissue residency markers. IL2C-trimeric pre-treatment prevented neutrophil influx during vaginal challenge with both nonoxynol-9 (N-9) and Mobiluncus mulieris, but maintenance of E-cadherin expression and barrier integrity was only observed for M. mulieris and not N-9. Depletion of FoxP3⁺Tregs reversed the protective effects of IL2C-trimeric. Thus, induction of Tregs could be a potential strategy to regulate genital inflammation, reduce HIV acquisition risk, and improve reproductive health outcomes in women.

生殖器炎症与艾滋病毒风险增加有关。我们之前发现宫颈内Tregs与生殖器炎症减少和HIV靶细胞减少相关。IL-2诱导Tregs，临床正在努力增强其调节活性。在本研究中，在雌性FoxP3GFP小鼠中腹腔注射IL-2与IL-2mAb克隆JES6-1A12 （il2c -三聚体）结合的IL-2，选择性地扩大了雌性下生殖道的treg细胞，对非treg细胞的影响有限。il2c三聚体增加了treg上GITR的表达，大多数treg表达组织驻留标记。il - 2 -三聚体预处理可阻止壬氧醇-9 （N-9）和莫Mobiluncus muleris阴道攻击期间中性粒细胞内流，但仅在莫mobilunus muleris中观察到E-cadherin表达和屏障完整性的维持，而在N-9中则没有。FoxP3+Tregs的缺失逆转了il2c三聚体的保护作用。因此，诱导Tregs可能是调节生殖器炎症、降低艾滋病毒感染风险和改善妇女生殖健康结果的潜在策略。

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引用次数: 0

Erratum to “Single cell transcriptional analysis of human adenoids identifies molecular features of airway microfold cells”. [Mucosal Immunol. 18(5) (2025) 1199–1217] “人腺样体单细胞转录分析鉴定气道微褶细胞的分子特征”的勘误。黏膜免疫，18(5)(2025)1199-1217。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Mucosal Immunology

Pub Date : 2025-12-01 DOI: 10.1016/j.mucimm.2025.10.006

Samuel Alvarez-Arguedas , Khadijah Mazhar , Andi Wangzhou , Ishwarya Sankaranarayanan , Gabriela Gaona , John T. Lafin , Ron B. Mitchell , Theodore J. Price , Michael U. Shiloh

引用次数: 0

CREB-mediated sensing of bacterial membrane vesicles unveils a conserved host defense pathway creb介导的细菌膜囊泡传感揭示了一个保守的宿主防御途径。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Mucosal Immunology

Pub Date : 2025-12-01 DOI: 10.1016/j.mucimm.2025.08.007

Saifei Wang, Bohan Qi, Chunyu Du, Peng Ma, Yao Zhang, Shuxin Chen, E Tian, Hansong Deng

Bacterial membrane vesicles (MVs) are critical mediators of virulence factor delivery and intercellular communication, yet the mechanisms by which hosts detect and respond to these vesicles remain poorly characterized. Through transcriptional profiling, we found that MVs derived from the non-lethal pathogenic Erwinia carotovora carotovora 15 (Ecc15) robustly induce reactive oxygen species (ROS) production and systemically upregulate Jon genes—a family of immune-related genes—in the Drosophila intestine 24 h post-infection. Strikingly, these effects contrast with transcriptional changes observed upon gut-specific overexpression of CRTC, the coactivator of the conserved transcription factor cAMP response element-binding protein (CREB). Intriguingly, ingestion of OMVs from Ecc15 or from the Gram-positive bacterium Lactobacillus plantarum (L.plantarum) significantly suppresses CREB activity in enterocytes (ECs). Fractionation experiments revealed that proteinaceous components within bacterial MVs inhibited CREB activity by reducing apical Ca²⁺ levels in ECs. Mechanistically, the CRTC/CREB cascade promoted gut microbial load by transcriptionally repressing PGRP-SC2-dependent amidase activity, a pathway independent of the canonical Relish/Imd signaling axis. Furthermore, OMVs from E. coli (BL21) also potently suppressed expression of pro-inflammatory factors, such as IL-6 and CXCL10 in NIH3T3 by blocking the activity of CREB. Collectively, these findings demonstrated that CREB play a conserved role on sense bacterial MVs and trigger anti-infection defenses in both Drosophila and mammalian systems, unveiling a novel paradigm in host-microbe communication.

细菌膜囊泡（MVs）是毒力因子传递和细胞间通讯的重要介质，但宿主检测和响应这些囊泡的机制仍不清楚。通过转录谱分析，我们发现来自非致死性致病性鹿角菌15 （ec15）的MVs在感染后24 h强烈诱导活性氧（ROS）的产生，并系统性上调果蝇肠道中Jon基因（一个免疫相关基因家族）。引人注目的是，这些影响与肠道特异性过表达CRTC（保守转录因子cAMP反应元件结合蛋白（CREB）的共激活因子）时观察到的转录变化形成对比。有趣的是，摄入来自Ecc15或革兰氏阳性细菌植物乳杆菌（l.p ultarum）的omv可显著抑制肠细胞（ECs）中的CREB活性。分离实验表明，细菌mv中的蛋白质成分通过降低ECs的顶端Ca2+水平来抑制CREB活性。从机制上讲，CRTC/CREB级联通过转录抑制pgrp - sc2依赖性氨基酶活性来促进肠道微生物负荷，这是一种独立于典型的调味品/Imd信号轴的途径。此外，来自大肠杆菌的omv （BL21）还通过阻断CREB的活性，有效抑制NIH3T3中IL-6和CXCL10等促炎因子的表达。总的来说，这些发现表明CREB在感知细菌mv和触发抗感染防御方面发挥保守作用，在果蝇和哺乳动物系统中揭示了宿主-微生物通信的新范式。

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引用次数: 0

Leukotriene B4 regulates T cell recognition and control of MCMV in mucosal tissues 白三烯B4调节粘膜组织中T细胞识别和MCMV的控制。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Mucosal Immunology

Pub Date : 2025-12-01 DOI: 10.1016/j.mucimm.2025.08.002

Lauren E. Springer , Han-Zhi Rao , Oliver Abinader , Ramkrishna Mitra , Christopher M. Snyder

Lipid mediators play important, yet poorly understood roles in regulating immune responses. Cytomegalovirus (CMV) is a herpesvirus that persists in mucosal tissues. Prior work suggests that leukotrienes, a class of inflammatory lipid mediators, contribute to viral control. Infection with murine (M)CMV altered leukotriene and other lipid mediator production in the nasal mucosa, lungs and salivary glands of mice. Mice lacking the receptor for leukotriene B4 (BLT1^−/−) had increased viral titers at early timepoints in the nasal mucosa and lungs and produced less interferon (IFN)-γ in both tissues, altering the balance between IFN-γ and interleukin (IL)-10. Importantly, viral control in BLT1^−/− mice was restored by IL-10 blockade, showing that leukotriene B4 promotes an optimal IFN-γ/IL-10 balance in these mucosal sites during acute infection. BLT1^−/− T cells showed no defects in the ability to produce IFN-γ, but their gene expression profiles suggested reduced activation and altered migratory capacity. MCMV-specific T cells compete for access to infected cells. Remarkably, when in competition with wild-type T cells, BLT1^−/− T cells competed poorly for antigen, resulting in reduced expansion. These data suggest that leukotriene B4 promotes control of CMV by optimizing T cell encounters with infected targets, maintaining the balance between IFN-γ and IL-10.

脂质介质在调节免疫反应中发挥着重要的作用，但人们对其知之甚少。巨细胞病毒（CMV）是一种持续存在于粘膜组织的疱疹病毒。先前的研究表明，白三烯，一类炎性脂质介质，有助于病毒控制。小鼠(M)巨细胞病毒感染改变了小鼠鼻黏膜、肺和唾液腺中白三烯和其他脂质介质的产生。缺乏白三烯B4 （BLT1-/-）受体的小鼠在鼻黏膜和肺部的早期时间点病毒滴度增加，在这两个组织中产生较少的干扰素(IFN)-γ，改变了干扰素-γ和白细胞介素(IL)-10之间的平衡。重要的是，通过IL-10阻断，BLT1-/-小鼠的病毒控制得以恢复，这表明白三烯B4在急性感染期间促进了这些粘膜部位的最佳IFN-γ/IL-10平衡。BLT1-/- T细胞在产生IFN-γ的能力上没有缺陷，但它们的基因表达谱表明激活降低，迁移能力改变。mcmv特异性T细胞竞争进入感染细胞。值得注意的是，当与野生型T细胞竞争时，BLT1-/- T细胞对抗原的竞争很差，导致扩增减少。这些数据表明，白三烯B4通过优化T细胞与感染靶标的接触，维持IFN-γ和IL-10之间的平衡，促进CMV的控制。

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引用次数: 0

Rhinovirus C15 infection induces airway epithelial cell remodeling and robust inflammatory responses: Potential implications for airway obstruction in children 鼻病毒C15感染诱导气道上皮细胞重塑和强烈的炎症反应：对儿童气道阻塞的潜在影响

IF 7.6 2区医学 Q1 IMMUNOLOGY

Mucosal Immunology

Pub Date : 2025-12-01 DOI: 10.1016/j.mucimm.2025.09.002

Yiran Li , Shilpi Singh , Hannah L. Briggs , Jordan E. Kreger , Alex L. Sliwicki , Emily L. Eberhardt , Shiuhyang Kuo , Jessica A. Czapla , J. Kelley Bentley , Heidi R. Flori , Amjad Horani , Steven L. Brody , Marc B. Hershenson

Despite recognition of rhinovirus-C (RV-C) as a cause of severe respiratory exacerbations, little is known about the pathogenesis of RV-C infections. We infected mucociliary-differentiated primary tracheobronchial epithelial cells with RV-C15 or RV-A16. Initial RNASeq data showed that, compared to RV-A16, RV-C15 decreased expression of genes related to ciliary function while increasing expression of genes associated with mucus secretion and inflammation. Using different airway epithelial cell isolates, we confirmed greater reduction in DNAI2 and FOXJ1 (regulates production of motile cilia) and increased FOXA3 (regulates mucin −related gene expression) after RV-C15 infection compared to RV-A16. Similarly, nasal swab samples from children with RV-C but not RV-A infections showed significantly decreased DNAI2 and FOXJ1 mRNA compared to controls. While both RV-C15 and RV-A16 infection of airway epithelial cells increased mRNA expression and secretion of MUC5AC, RV-C15 induced greater airway surface liquid thickness, as measured by FITC-dextran staining. DAPT, a Notch inhibitor, reversed the effects of RV-C15 on DNAI2, FOXJ1 and FOXA3 expression. RV-C15 induced loss of α-acetyl tubulin, extrusion of airway epithelial cells, dissociation of ZO-1 from tight junctions, reduced ciliary beat frequency and decreased epithelial cell transepithelial electrical resistance. Finally, protein abundance of pro-inflammatory cytokines in cell supernatants and nasal samples also tended to be higher after RV-C infection. We conclude that RV-C causes significant disruptions in airway epithelial cell ciliary function which may lead to airway obstruction. Such disruptions may play a role in the severity of RV-C respiratory tract infections.

尽管人们认识到鼻病毒- c （RV-C）是严重呼吸系统恶化的原因，但对RV-C感染的发病机制知之甚少。我们用RV-C15或RV-A16感染粘膜纤毛分化的原代气管支气管上皮细胞。初始RNASeq数据显示，与RV-A16相比，RV-C15减少了纤毛功能相关基因的表达，而增加了粘液分泌和炎症相关基因的表达。使用不同的气道上皮细胞分离物，我们证实，与RV-A16相比，RV-C15感染后DNAI2和FOXJ1（调节运动性纤毛的产生）的减少更大，FOXA3（调节粘蛋白相关基因表达）的增加更大。同样，与对照组相比，感染RV-C但未感染RV-A的儿童的鼻拭子样本显示DNAI2和FOXJ1 mRNA显著降低。通过fitc -葡聚糖染色检测，虽然RV-C15和RV-A16感染气道上皮细胞均增加mRNA表达和MUC5AC分泌，但RV-C15诱导气道表面液体厚度增加。Notch抑制剂DAPT逆转了RV-C15对DNAI2、FOXJ1和FOXA3表达的影响。RV-C15诱导α-乙酰基小管蛋白缺失，气道上皮细胞挤压，ZO-1与紧密连接分离，睫状搏动频率降低，上皮细胞经上皮电阻降低。最后，病毒感染后，细胞上清液和鼻腔样本中促炎细胞因子的蛋白丰度也趋于较高。我们得出结论，RV-C引起气道上皮细胞纤毛功能的显著破坏，这可能导致气道阻塞。这种破坏可能在RV-C呼吸道感染的严重程度中发挥作用。

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引用次数: 0