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Acquired tick resistance in Peromyscus leucopus alters Ixodes scapularis infection. 获得性蜱抗药性改变肩胛骨硬蜱感染。
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-14 Epub Date: 2025-09-03 DOI: 10.1128/iai.00246-25
Elis A Fisk, Cassie J Leonard, Kristin L Rosche, Elisabeth Ramirez-Zepp, Jeffrey R Abbott, Jeb P Owen, Dana K Shaw

Ticks are obligate hematophagous parasites and pathogen vectors responsible for morbidity and mortality worldwide. Ixodes scapularis is a vector for at least seven pathogens relevant to human and animal health, including the Lyme disease microbe, Borrelia burgdorferi, and the causative agent of anaplasmosis, Anaplasma phagocytophilum. Tick-host interactions affect the maintenance of tick-borne pathogens in a population. Here, we report that repeated I. scapularis larval infestations on the wild host species Peromyscus leucopus lead to immune-mediated rejection of the tick, a phenomenon termed acquired tick resistance (ATR). On previously infested mice, we observed that larval feeding success was reduced by over 50%, and fed larvae had decreased blood meal weights compared to larvae fed on naïve hosts. Over sequential infestations, mice exhibited increasingly severe inflammation at tick bite sites characterized by an influx of basophils, eosinophils, neutrophils, and T lymphocytes. Larvae fed on sensitized mice ingested higher quantities of host leukocytes when compared to ticks fed on naïve hosts, which rarely ingested nucleated cells. When challenged with B. burgdorferi or A. phagocytophilum, larvae fed on sensitized mice ingested more bacteria. Altogether, we demonstrate that reservoir host species develop ATR against larval I. scapularis, which reduces tick feeding success and affects pathogen ingestion by larvae. These results indicate that ATR could impact Ixodes population dynamics, prevalence of infected ticks, and pathogen circulation in the wild.

蜱是专性吸血寄生虫和病原体媒介,在世界范围内造成发病率和死亡率。肩胛棘虫是至少七种与人类和动物健康相关的病原体的媒介,包括莱姆病微生物、伯氏疏螺旋体和无形体病的病原体、嗜吞噬细胞无形体。蜱与宿主的相互作用影响种群中蜱传病原体的维持。在这里,我们报告了反复的肩胛骨蜱幼虫对野生宿主白斑过omyscus leucopus的侵害导致免疫介导的对蜱的排斥,这种现象被称为获得性蜱抗性(ATR)。在先前被感染的小鼠中,我们观察到幼虫的取食成功率降低了50%以上,并且与以naïve宿主为食的幼虫相比,被喂食的幼虫的血粉重量降低了。在连续的感染中,小鼠在蜱叮咬部位表现出越来越严重的炎症,其特征是嗜碱性粒细胞、嗜酸性粒细胞、中性粒细胞和T淋巴细胞的涌入。与以naïve宿主为食的蜱虫相比,以致敏小鼠为食的幼虫摄入了更多的宿主白细胞,而naïve宿主很少摄入有核细胞。当被伯氏疏螺旋体或嗜吞噬细胞芽胞杆菌攻击时,以致敏小鼠为食的幼虫摄入了更多的细菌。综上所述,我们证明了宿主物种对肩胛骨蜱幼虫产生ATR,这降低了蜱的取食成功率,并影响了幼虫对病原体的摄入。这些结果表明,ATR可能会影响野外伊蚊种群动态、感染蜱流行和病原体循环。
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引用次数: 0
Complete deletion of the Chlamydia muridarum putative cytotoxin locus reveals contributions during invasion in tissue culture and oviduct pathology during murine genital tract infection. muridarum衣原体假定的细胞毒素位点的完全缺失揭示了在组织培养和小鼠生殖道感染期间的输卵管病理侵袭过程中的贡献。
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-14 Epub Date: 2025-09-22 DOI: 10.1128/iai.00419-25
Lucie H Berclaz, Gracie Eicher, Grace Wieselquist, Akosua Frimpong, Aria Mallare, Rebeccah S Lijek, Kenneth A Fields

Chlamydiaceae is a family of obligate intracellular bacteria that infect a wide range of human and animal hosts. Chlamydia muridarum is a murine-specific species that has been leveraged as an efficacious model of disease mediated by human-specific Chlamydia trachomatis. Genes within the plasticity zone, a region of the chromosome with increased genetic variation across species and serovars, are speculated to contribute to species-specific pathogenesis. C. muridarum expresses three homologous proteins (TC0437-0439) that show similarity to large clostridial cytotoxins. The putative chlamydial cytotoxins have been proposed to mediate immediate toxicity in highly infected epithelial cells by interfering with actin polymerization. We utilized FRAEM mutagenesis to delete all three putative cytotoxins (tc0437-0439). The null strain retained immediate cytotoxicity but exhibited decreased invasion efficiency in tissue culture. During murine infections of the female genital tract, the absence of the putative cytotoxins caused decreased oviduct pathology and did not impact bacterial burden in the upper genital tract. These results indicate that the putative cytotoxins contribute to infection at the cellular level and in the female genital tract of mice.

衣原菌科是一类专性细胞内细菌,广泛感染人类和动物宿主。沙眼衣原体是一种小鼠特异性物种,已被利用作为人类特异性沙眼衣原体介导的疾病的有效模型。可塑性区是染色体上的一个区域,在物种和血清型中遗传变异增加,据推测,可塑性区内的基因有助于物种特异性发病。C. muridarum表达三个同源蛋白(TC0437-0439),显示出与大型梭状芽胞杆菌细胞毒素相似。假设的衣原体细胞毒素通过干扰肌动蛋白聚合介导高度感染上皮细胞的立即毒性。我们利用FRAEM诱变法删除了所有三种假定的细胞毒素(tc0437-0439)。空白菌株在组织培养中保留了立即的细胞毒性,但表现出较低的侵袭效率。在雌性生殖道感染的小鼠中,假定的细胞毒素的缺失导致输卵管病理减少,并且不影响上生殖道的细菌负荷。这些结果表明,假定的细胞毒素在细胞水平和小鼠雌性生殖道中参与感染。
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引用次数: 0
Elevated glucose increases Staphylococcus aureus antibiotic resistance in a cystic fibrosis airway epithelial cell infection model. 在囊性纤维化气道上皮细胞感染模型中,葡萄糖升高会增加金黄色葡萄球菌的抗生素耐药性。
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-14 Epub Date: 2025-09-22 DOI: 10.1128/iai.00178-25
Emily M Hughes, Meghan J Hirsch, Joshua T Huffines, Stefanie Krick, Megan R Kiedrowski

In a healthy lung, the airway epithelium regulates glucose transport to maintain low glucose concentrations in the airway surface liquid (ASL). However, hyperglycemia and chronic lung diseases, such as cystic fibrosis (CF), can result in increased glucose in bronchial aspirates. People with CF are also at increased risk of lung infections caused by bacterial pathogens, including methicillin-resistant Staphylococcus aureus. Yet, it is not known how increased airway glucose availability affects bacteria in chronic CF lung infections or impacts treatment outcomes. To model the CF airways, we cultured immortalized CF (CFBE41o-) and non-CF (16HBE) human bronchial epithelial cells at the air-liquid interface (ALI). Glucose concentrations in the basolateral media were maintained at 5.5 or 12.5 mM to mimic a normal and hyperglycemic milieu, respectively. We found that glucose concentrations in the ASL of ALI cultures maintained in normal or high glucose mimicked levels measured in breath condensate assays from people with CF and hyperglycemia. Additionally, we found hyperglycemia increased S. aureus aggregation and antibiotic resistance during infection of cells maintained in high glucose compared to normal glucose conditions. Heightened antibiotic resistance was not observed during in vitro growth with elevated glucose. Limiting glucose with 2-deoxyglucose both decreased aggregation and reduced antibiotic resistance back to levels comparable to non-hyperglycemic conditions. These data indicate that hyperglycemia alters S. aureus growth during infection and may reduce efficacy of antibiotic treatment. Glucose restriction is a potential option that could be explored to limit bacterial growth and improve treatment outcomes in chronic airway infections.

在健康的肺中,气道上皮调节葡萄糖转运以维持气道表面液体(ASL)中的低葡萄糖浓度。然而,高血糖和慢性肺部疾病,如囊性纤维化(CF),可导致支气管吸入物中葡萄糖升高。CF患者还面临由细菌性病原体(包括耐甲氧西林金黄色葡萄球菌)引起的肺部感染风险增加。然而,尚不清楚气道葡萄糖可用性增加如何影响慢性CF肺部感染的细菌或影响治疗结果。为了建立CF气道模型,我们在气液界面(ALI)处培养永生化CF (cfbe410 -)和非CF (16HBE)人支气管上皮细胞。将基底外侧培养基中的葡萄糖浓度分别维持在5.5或12.5 mM,以模拟正常和高血糖环境。我们发现ALI培养的ASL中的葡萄糖浓度维持在正常或高葡萄糖水平,与CF和高血糖患者的呼吸凝结水测定的水平相似。此外,我们发现与正常葡萄糖条件相比,高血糖增加了金黄色葡萄球菌在高葡萄糖条件下维持的细胞感染期间的聚集和抗生素耐药性。在葡萄糖升高的体外生长过程中,没有观察到抗生素耐药性的增强。用2-脱氧葡萄糖限制葡萄糖既可以减少聚集,又可以将抗生素耐药性降低到与非高血糖状况相当的水平。这些数据表明,高血糖会改变金黄色葡萄球菌在感染期间的生长,并可能降低抗生素治疗的疗效。葡萄糖限制是一种潜在的选择,可以探索限制细菌生长和改善慢性气道感染的治疗效果。
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引用次数: 0
Myeloid cell-specific type I interferon signaling mediates age-dependent inflammation and protection in Bordetella pertussis infection. 髓细胞特异性I型干扰素信号介导百日咳杆菌感染的年龄依赖性炎症和保护。
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-14 Epub Date: 2025-09-22 DOI: 10.1128/iai.00306-25
Amit Kumar, Alicia Bukowski, Nicholas H Carbonetti

Type I interferons (IFNs) play complex roles during bacterial infections. We previously found that type I IFNs were induced in Bordetella pertussis-infected adult mice but not in infant mice, a potentially relevant clinical dichotomy, since pertussis can be fatal in human infants. We investigated the role of type I IFNs and their cross-regulation with type III IFNs (IFN-λ) in B. pertussis infection across developmental stages. In contrast to global IFNAR1 knockout adult mice, in which lung inflammation was equivalent to that in wild-type mice, myeloid cell-specific deficiency of the type I IFN receptor protein IFNAR1 (LysMCreIFNAR1fl/fl) resulted in significantly reduced lung inflammation and pro-inflammatory cytokine production, despite elevated pulmonary IFN-λ levels. Mechanistically, we found that, in contrast to WT macrophages, IFNAR1-deficient macrophages produced IFN-λ in response to B. pertussis or pertussis toxin, a process dependent on the G protein-coupled receptor lysophosphatidic acid receptor 1 (LPAR1). IFNAR1 deficiency did not affect type I IFN expression or killing capacity by macrophages and neutrophils. In striking contrast to WT infant mice, which developed resistance to lethal B. pertussis infection by postnatal day 10 (P10), LysMCreIFNAR1fl/fl infant mice remained highly susceptible to lethal infection through P21, exhibiting increased lung bacterial burden and inflammation, as well as increased bacterial dissemination compared to WT infant mice. These findings reveal a critical age- and cell-specific interplay between type I and III IFNs during B. pertussis infection and highlight a novel LPAR1-dependent pathway for IFN-λ induction in the absence of type I IFN signaling.

I型干扰素(ifn)在细菌感染过程中发挥着复杂的作用。我们之前发现I型干扰素在感染百日咳博德泰拉的成年小鼠中被诱导,但在幼鼠中却没有,这是一个潜在的相关临床二分法,因为百日咳在人类婴儿中是致命的。我们研究了I型IFN及其与III型IFN (IFN-λ)在不同发育阶段百日咳感染中的交叉调节作用。与IFNAR1基因敲除的成年小鼠相比,其肺部炎症与野生型小鼠相当,尽管肺部IFN-λ水平升高,但髓细胞特异性缺乏I型IFN受体蛋白IFNAR1 (LysMCreIFNAR1fl/fl)导致肺部炎症和促炎细胞因子的产生显著减少。在机制上,我们发现,与WT巨噬细胞相比,ifnar1缺陷的巨噬细胞在对百日咳或百日咳毒素的反应中产生IFN-λ,这一过程依赖于G蛋白偶联受体溶血磷脂酸受体1 (LPAR1)。IFNAR1缺乏不影响I型IFN的表达或巨噬细胞和中性粒细胞的杀伤能力。与出生后第10天(P10)对致命性百日破感染产生抗性的WT幼鼠形成鲜明对比的是,LysMCreIFNAR1fl/fl幼鼠通过P21仍然对致命性感染高度敏感,与WT幼鼠相比,表现出肺部细菌负担和炎症增加,以及细菌传播增加。这些发现揭示了百日咳感染期间I型和III型IFN之间的关键年龄和细胞特异性相互作用,并强调了在缺乏I型IFN信号传导的情况下,一种新的依赖lpar1的IFN-λ诱导途径。
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引用次数: 0
Staphylococcus aureus transcriptomics and single-cell sequencing approaches. 金黄色葡萄球菌转录组学和单细胞测序方法。
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-14 Epub Date: 2025-09-15 DOI: 10.1128/iai.00411-25
Natalia Malachowa, Frank R DeLeo

Staphylococcus aureus is an important cause of human infections globally and ranks among the top causes of death by bacteria. In addition, the microbe is notorious for developing resistance to antibiotics. Methicillin-resistant S. aureus is endemic in healthcare facilities and the community in many regions of the world. Although our understanding of S. aureus as a human commensal organism and opportunistic pathogen remains incomplete, the use of genomics and transcriptomics approaches for S. aureus research has advanced this knowledge significantly over the past 20 years. This article reviews genomics approaches, with special emphasis on transcriptomics and single-cell sequencing, used to study S. aureus, past and present, and highlights selected discoveries made with these methods and new applications moving forward.

金黄色葡萄球菌是全球人类感染的一个重要原因,也是细菌致死的主要原因之一。此外,这种微生物因对抗生素产生耐药性而臭名昭著。耐甲氧西林金黄色葡萄球菌在世界许多地区的卫生保健机构和社区中流行。虽然我们对金黄色葡萄球菌作为人类共生生物和机会性病原体的了解仍然不完整,但在过去的20年里,基因组学和转录组学方法在金黄色葡萄球菌研究中的应用显著地提高了这方面的知识。本文回顾了基因组学方法,特别强调转录组学和单细胞测序,过去和现在用于研究金黄色葡萄球菌,并重点介绍了这些方法和新应用的发现。
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引用次数: 0
Listeria monocytogenes adenosine auxotrophs are impaired for intracellular and extracellular growth but retain potent immunogenicity. 单核细胞增生李斯特菌腺苷营养不良的细胞内和细胞外生长受损,但保留有效的免疫原性。
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-14 Epub Date: 2025-09-05 DOI: 10.1128/iai.00343-25
Ying Feng, Mariya Lobanovska, Jenna Vickery, Jesse Garcia Castillo, Leslie Güereca, Shannon K Chang, Michel DuPage, Daniel A Portnoy

Listeria monocytogenes is a facultative intracellular pathogen that has garnered attention as a potential cancer therapeutic due to its ability to induce robust cell-mediated immunity. To ensure safe clinical administration, deletion of certain genes, such as actA, has been used to attenuate L. monocytogenes-based vaccine strains while preserving immunogenicity. Here we explored the potential inclusion of a purA gene deletion to enhance the development of L. monocytogenes-based immunotherapy. The purA gene encodes adenylosuccinate synthetase, which catalyzes the conversion of inosine monophosphate to adenosine monophosphate (AMP), a critical step in the de novo biosynthesis of purines. Since nucleotide biosynthesis is critical for the survival and pathogenesis of many bacterial pathogens, we examined the requirements of L. monocytogenes AMP synthesis in tissue culture and animal infection models. The purA mutants were able to escape from phagosomes of bone marrow-derived macrophages but were highly defective for subsequent growth in the host cell cytosol. In contrast to wild-type bacteria, the mutants did not grow in human serum or sheep blood. In intravenously infected mice, purA mutants were highly attenuated, similar to actA mutants, but displayed distinct growth kinetics during the course of infection. Remarkably, the purA mutants exhibited different localization patterns across splenic immune cells and elicited a more potent CD8+ T-cell response compared to actA mutants. These results underscore the essentiality of AMP biosynthesis for L. monocytogenes pathogenesis and provide new avenues for developing safe L. monocytogenes-based vaccines and therapeutics.

单核细胞增生李斯特菌是一种兼性细胞内病原体,由于其诱导强大的细胞介导免疫的能力,作为一种潜在的癌症治疗药物而引起了人们的关注。为了确保临床给药安全,已采用删除某些基因(如actA)来减毒单细胞增生乳杆菌疫苗菌株,同时保持免疫原性。在这里,我们探讨了purA基因缺失的潜在包含,以促进单核细胞增生乳杆菌为基础的免疫治疗的发展。purA基因编码腺苷琥珀酸合成酶,该合成酶催化单磷酸肌苷转化为单磷酸腺苷(AMP),这是嘌呤从头合成的关键步骤。由于核苷酸的生物合成对许多细菌病原体的生存和发病至关重要,我们研究了单核增生乳杆菌在组织培养和动物感染模型中合成AMP的需求。purA突变体能够从骨髓源性巨噬细胞的吞噬体中逃脱,但在宿主细胞质中随后的生长存在高度缺陷。与野生型细菌相比,突变体不能在人类血清或绵羊血液中生长。在静脉注射感染的小鼠中,purA突变体高度减弱,与actA突变体相似,但在感染过程中表现出明显的生长动力学。值得注意的是,purA突变体在脾脏免疫细胞中表现出不同的定位模式,与actA突变体相比,引发了更有效的CD8+ t细胞应答。这些结果强调了AMP生物合成在单核增生乳杆菌发病机制中的重要性,并为开发基于单核增生乳杆菌的安全疫苗和治疗方法提供了新的途径。
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引用次数: 0
Inhibition of RND-mediated efflux attenuates antibiotic resistance and virulence in hypervirulent Klebsiella pneumoniae. 抑制rnd介导的外排可减轻高致病性肺炎克雷伯菌的抗生素耐药性和毒力。
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-14 Epub Date: 2025-09-22 DOI: 10.1128/iai.00301-25
Mia E Van Allen, Yuding Weng, X Renee Bina, James E Bina

Klebsiella pneumoniae (Kp) is a major human pathogen causing hospital-acquired and community-acquired infections with emerging hypervirulent strains (hvKp) posing a significant threat due to its ability to cause severe invasive infections in healthy individuals. In addition to antimicrobial resistance, virulence factors including capsule production, biofilm formation, and iron acquisition systems are critical for hvKp pathogenesis. In this study, we investigated how resistance-nodulation-division (RND)-family efflux systems contribute to antimicrobial resistance and virulence in hvKp strain KPPR1 using the RND-specific inhibitor phenyl-arginine β-naphthylamide (PAβN). We found that PAβN treatment rendered KPPR1 more susceptible to multiple antibiotics while simultaneously attenuating virulence factor production. PAβN significantly reduced capsule biosynthetic gene expression, resulting in decreased uronic acid levels, hypermucoviscosity, and biofilm formation. PAβN also impaired growth under iron-limited conditions, suggesting RND-mediated efflux contributes to iron acquisition. PAβN-dependent virulence attenuation was demonstrated through reduced KPPR1 adherence to cultured intestinal enterocytes and decreased pathogenicity in the Galleria mellonella infection model compared to untreated controls. Collectively, these results demonstrate that RND-mediated efflux is critical for both antimicrobial resistance and virulence in hvKp strain KPPR1. Our findings establish RND efflux inhibitors as promising dual-target therapeutics that can simultaneously combat antibiotic resistance and attenuate virulence in hvKp infections.

肺炎克雷伯菌(Kp)是一种主要的人类病原体,引起医院获得性和社区获得性感染,其中新出现的高毒力菌株(hvKp)由于能够在健康个体中引起严重的侵袭性感染而构成重大威胁。除了抗菌素耐药性外,毒力因素包括胶囊生产、生物膜形成和铁获取系统对hvKp的发病至关重要。在这项研究中,我们利用RND特异性抑制剂苯基精氨酸β-萘酰胺(PAβN)研究了耐药结核分裂(RND)家族外排系统如何促进hvKp菌株KPPR1的抗微生物药物耐药性和毒力。我们发现PAβN处理使KPPR1对多种抗生素更敏感,同时减少毒力因子的产生。PAβN显著降低胶囊生物合成基因表达,导致糖醛酸水平降低、高粘滞和生物膜形成。PAβN在铁限制条件下也会损害生长,这表明rnd介导的外排有助于铁的获取。与未处理的对照组相比,通过减少KPPR1对培养的肠道肠细胞的粘附和降低mellonella感染模型的致病性,证实了pa β n依赖性毒力衰减。总之,这些结果表明,rnd介导的外排对hvKp菌株KPPR1的抗微生物药物耐药性和毒力都至关重要。我们的研究结果表明,RND外排抑制剂是一种有希望的双靶点治疗药物,可以同时对抗抗生素耐药性和减弱hvKp感染的毒力。
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引用次数: 0
Lymphotoxin beta receptor-/- mice display altered B- and T-cell subpopulations in the bone marrow and peritoneal cavity after Toxoplasma gondii infection. 刚地弓形虫感染后,淋巴蛋白β受体小鼠骨髓和腹腔内的B细胞和t细胞亚群发生改变。
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-14 Epub Date: 2025-09-09 DOI: 10.1128/iai.00408-25
Marcel Helle, Ursula R Sorg, Johannes Ptok, Rachel E Thomas, Katharina Pracht, Patrick Petzsch, Alain de Bruin, Hans-Martin Jäck, Karl Köhrer, Daniel Degrandi, Klaus Pfeffer

Lymphotoxin β receptor (LTβR/TNFRSF3) signaling plays a crucial role in immune defense. Notably, LTβR-deficient (LTβR-/-) mice exhibit severe defects in innate and adaptive immunity against various pathogens and succumb to Toxoplasma gondii infection. Here, we investigated the bone marrow (BM) and peritoneal cavity (PerC) compartments of LTβR-/- mice during T. gondii infection, demonstrating perturbed B-cell and T-cell subpopulations in the absence of LTβR signaling. T. gondii infection disrupted BM lymphopoiesis, depleting early and mature B cells in WT mice, whereas mature B cells remained present in LTβR-/- BM. LTβR-/- BM also exhibited reduced MHCII+ monocytes and a plasma cell compartment skewed toward IgM+ rather than IgA+ cells. In addition, BM Tcell subsets were altered, exhibiting decreased double-negative (CD4-/CD8-) and increased CD4+ and CD8+ T-cell frequencies. Analysis of the BM transcriptome revealed diminished interferon responses but an upregulated TNFα-NF-κB signaling signature in uninfected and infected LTβR-/- mice, potentially compensating for the absence of LTβR signaling. LTβR-/- mice displayed an altered B-1a to B-1b ratio and a predominant presence of neutrophils in the PerC. In summary, we identified novel immunological alterations in the BM and PerC compartments of LTβR-/- mice, which suggest new roles for LTβR signaling in B- and T-cell homeostasis, migration, and pathogen defense.

淋巴素β受体(LTβR/TNFRSF3)信号在免疫防御中起着至关重要的作用。值得注意的是,LTβR-缺陷(LTβR-/-)小鼠对各种病原体表现出严重的先天和适应性免疫缺陷,并死于弓形虫感染。在这里,我们研究了弓形虫感染期间LTβR-/-小鼠的骨髓(BM)和腹腔(PerC)区室,发现在LTβR信号缺失的情况下,b细胞和t细胞亚群受到干扰。弓形虫感染破坏了BM的淋巴细胞生成,在WT小鼠中消耗了早期和成熟的B细胞,而在LTβR-/- BM中成熟的B细胞仍然存在。LTβR-/- BM也表现出MHCII+单核细胞减少,浆细胞室倾向于IgM+而不是IgA+细胞。此外,BM t细胞亚群发生改变,双阴性(CD4-/CD8-)减少,CD4+和CD8+ t细胞频率增加。BM转录组分析显示,在未感染和感染LTβR-/-小鼠中,干扰素反应减弱,但TNFα-NF-κ b信号信号上调,可能弥补了LTβR信号的缺失。LTβR-/-小鼠表现出B-1a与B-1b比例的改变和PerC中中性粒细胞的主要存在。总之,我们在LTβR-/-小鼠的BM和PerC区室中发现了新的免疫学改变,这表明LTβR信号在B细胞和t细胞的稳态、迁移和病原体防御中发挥了新的作用。
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引用次数: 0
Evaluation of Mycoplasma mycoides subsp. mycoides antigens capable of stimulating host IRG-47 release identifies Mmm604, Mmm605, and Mmm606 as potential subunit vaccine antigens. 支原体亚种的评价。能够刺激宿主IRG-47释放的真菌抗原鉴定Mmm604、Mmm605和Mmm606为潜在的亚单位疫苗抗原。
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-14 Epub Date: 2025-09-09 DOI: 10.1128/iai.00186-25
Tong Liu, Huanjun Zhao, Qi Wu, Yukun Wei, Jiuqing Xin, Qiao Pan

Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides (Mmm), is a devastating cattle disease with high morbidity and mortality, threatening cattle productivity in Sub-Saharan Africa and potentially in parts of Asia. Cross-border livestock trade increases the risk of CBPP introduction or reintroduction. Current vaccines were developed from attenuated Mmm strains in the last century and face limitations regarding animal welfare, immunity duration, and adverse reactions, necessitating new vaccine strategies. Subunit vaccines offer a promising alternative, but identifying effective antigens is critical. Given the key role of cellular immunity in CBPP control, we focused on antigen identification that elicits a host cellular immune response. This study explores antigen candidates based on Ben-181, a vaccine that successfully eradicated CBPP in China. Ben-181 specifically induces interferon-γ (IFN-γ)-dependent IRG-47 expression, and IFN-γ correlates with cellular immune responses. We propose IRG-47 as a potential marker for Mmm antigen screening. Comparative genomic analysis between Ben-181 and the non-immunoprotective strain Ben-468 identified 35 proteins potentially linked to IRG-47 expression. Further screening revealed Mmm604, Mmm605, and Mmm606 as inducers of IRG-47 release. Intranasal immunization with these proteins in mice enhanced splenic lymphocyte proliferation, CD8 +T cell activation, a mixed Th1/Th2/Th17 response, and humoral antibody production. Mmm604 and Mmm606 also trigger mucosal antibody responses in mice. These proteins effectively stimulate cellular and humoral responses, making them promising candidates for Mmm subunit vaccine development. Our study highlights the potential of IRG-47 in Mmm antigen screening.

传染性牛胸膜肺炎(CBPP),由支原体引起。真菌病是一种具有高发病率和高死亡率的毁灭性牛病,威胁着撒哈拉以南非洲以及亚洲部分地区的牛生产力。跨境牲畜贸易增加了引入或再引入CBPP的风险。目前的疫苗是从上个世纪的Mmm减毒株中开发出来的,在动物福利、免疫持续时间和不良反应方面面临限制,需要新的疫苗策略。亚单位疫苗提供了一个很有希望的替代方案,但确定有效抗原至关重要。考虑到细胞免疫在CBPP控制中的关键作用,我们重点研究了引起宿主细胞免疫反应的抗原鉴定。本研究探索了基于Ben-181的候选抗原,Ben-181是一种在中国成功根除CBPP的疫苗。Ben-181特异性诱导干扰素-γ (IFN-γ)依赖的IRG-47表达,IFN-γ与细胞免疫应答相关。我们建议IRG-47作为筛选Mmm抗原的潜在标记物。比较基因组分析Ben-181和非免疫保护性菌株Ben-468,鉴定出35个可能与IRG-47表达相关的蛋白。进一步筛选发现Mmm604、Mmm605和Mmm606是IRG-47释放的诱导剂。小鼠鼻内免疫这些蛋白可增强脾淋巴细胞增殖、CD8 +T细胞活化、Th1/Th2/Th17混合反应和体液抗体的产生。Mmm604和Mmm606也能在小鼠中引发粘膜抗体反应。这些蛋白有效地刺激细胞和体液反应,使它们成为Mmm亚单位疫苗开发的有希望的候选者。我们的研究强调了IRG-47在Mmm抗原筛选中的潜力。
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引用次数: 0
Neonatal infection with Helicobacter pylori affects stomach and colon microbiome composition and gene expression in mice. 新生儿感染幽门螺杆菌影响小鼠胃和结肠微生物组成和基因表达。
IF 2.8 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-10-14 Epub Date: 2025-09-22 DOI: 10.1128/iai.00250-25
Katrine B Graversen, Bella Bjarnov-Nicolau, Sigri Kløve, Krístina Halajová, Sandra B Andersen

The stomach bacterium Helicobacter pylori is estimated to infect half of the world's population, and the health implications are affected by the age at infection. Neonatal H. pylori infection of mice is a relevant model to investigate metabolic and immunological effects. We performed an explorative study at the dynamic 1st month of life to compare the composition of the gastrointestinal tract microbiome and stomach gene expression of mice neonatally infected with H. pylori with that of uninfected mice. We found that H. pylori was present only in the stomach, and that H. pylori loads increase with age from 1 week after infection and onward, especially after weaning. Stomach and colon microbiome composition was strikingly similar between sites at the same sampling time but changed significantly over 1 week, with increased diversity at both sites. Despite the fact that the relative abundance of H. pylori in the stomach was low and never exceeded 3%, the composition and alpha diversity of the gastrointestinal microbiome was significantly affected by infection. In a pathway enrichment analysis, we found that stomach gene expression related to the extracellular matrix, muscle contraction, and metabolism was affected by infection. Expression of these key processes was, in infected mice, shifted away from that of control mice toward that of all mice sampled the subsequent week, which we speculate represents accelerated development in infected mice.

据估计,胃中的幽门螺杆菌感染了世界上一半的人口,其对健康的影响受感染年龄的影响。新生儿幽门螺杆菌感染是研究小鼠代谢和免疫影响的相关模型。我们在出生后1个月进行了一项探索性研究,比较了感染幽门螺杆菌的新生小鼠与未感染的新生小鼠胃肠道微生物组的组成和胃基因表达。我们发现幽门螺杆菌仅存在于胃中,并且从感染后1周开始,特别是断奶后,幽门螺杆菌的负荷随着年龄的增长而增加。在相同的采样时间,不同地点之间的胃和结肠微生物组组成惊人地相似,但在1周内变化显著,两个地点的多样性都有所增加。尽管胃中幽门螺杆菌的相对丰度较低,从未超过3%,但胃肠道微生物组的组成和α多样性受到感染的显著影响。在途径富集分析中,我们发现与细胞外基质、肌肉收缩和代谢相关的胃基因表达受到感染的影响。在感染小鼠中,这些关键过程的表达从对照组小鼠转移到随后一周采样的所有小鼠,我们推测这代表了感染小鼠的加速发育。
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Infection and Immunity
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