American Journal of Pathology最新文献

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Segmental regulation of intestinal motility by colitis and the adaptive immune system in the mouse ileum and colon. 小鼠回肠和结肠中结肠炎和适应性免疫系统对肠蠕动的节段性调控
IF 4.7 2区 医学
American Journal of Pathology Pub Date : 2024-11-17 DOI: 10.1016/j.ajpath.2024.10.020
Raquel Gomez-Bris, Pilar Rodríguez-Rodríguez, Marina Ortega-Zapero, Santiago Ruvira, Raquel Castillo-González, María Jesús Fernández-Aceñero, Aránzazu Cruz-Adalia, Angela Saez, Silvia-Magdalena Arribas, Jose-Maria Gonzalez-Granado
{"title":"Segmental regulation of intestinal motility by colitis and the adaptive immune system in the mouse ileum and colon.","authors":"Raquel Gomez-Bris, Pilar Rodríguez-Rodríguez, Marina Ortega-Zapero, Santiago Ruvira, Raquel Castillo-González, María Jesús Fernández-Aceñero, Aránzazu Cruz-Adalia, Angela Saez, Silvia-Magdalena Arribas, Jose-Maria Gonzalez-Granado","doi":"10.1016/j.ajpath.2024.10.020","DOIUrl":"https://doi.org/10.1016/j.ajpath.2024.10.020","url":null,"abstract":"<p><p>Gastrointestinal motility disturbances are a hallmark of inflammatory bowel disease (IBD); however, their mechanisms remain unclear. This study utilized a dextran sulfate sodium (DSS)-induced colitis mouse model, deficient in mature B and T lymphocytes, to assess intestinal motility and the role of the adaptive immune system in health and IBD. In healthy mice, the absence of adaptive lymphocytes reduced acetylcholine (ACh) sensitivity in the ileum. During colitis, it decreases motility by reducing the intensity and frequency of spontaneous contractions while increasing cholinergic responsiveness. In the proximal colon, adaptive immunity deficiency led to increased contractility and reduced ACh sensitivity in homeostasis, while colitis reduced contractile capacity. In the mid-colon, immune-deficient mice have reduced ACh sensitivity in homeostasis and exacerbated contractile responses during colitis. In the distal colon, adaptive immunity loss reduced contractility in health and cholinergic responsiveness during colitis. These motility alterations were associated with altered acetylcholinesterase and M2/M3 muscarinic receptor expression. Notably, adaptive lymphocyte deficiency resulted in reduced tissue damage and lower TNF-α expression in the colon during colitis paralleling intestinal motility changes. Overall, the adaptive immune system critically regulates motility and inflammation across different intestinal segments in IBD.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Amyloid Cascade Hypothesis: A Conclusion in Search of Support. 淀粉样蛋白级联假说:寻找支持的结论
IF 4.7 2区 医学
American Journal of Pathology Pub Date : 2024-11-10 DOI: 10.1016/j.ajpath.2024.10.014
Rudy J Castellani, Pouya Jamshidi, Germán Plascencia-Villa, George Perry
{"title":"The Amyloid Cascade Hypothesis: A Conclusion in Search of Support.","authors":"Rudy J Castellani, Pouya Jamshidi, Germán Plascencia-Villa, George Perry","doi":"10.1016/j.ajpath.2024.10.014","DOIUrl":"https://doi.org/10.1016/j.ajpath.2024.10.014","url":null,"abstract":"<p><p>The amyloid cascade hypothesis as the etiological underpinning of Alzheimer's disease (AD) is supported by a large body of literature, the most influential of which are genetic studies of the 1980's and 1990's. Other evidence includes the neuropathology of Down syndrome, apparent toxicity of oligomeric amyloid-β (Aβ), interactions with apolipoprotein E (APOE), and the analogy of cardiac amyloidosis. On the other hand, there is considerable phenotypic heterogeneity among the rare familial AD kindreds, which tempers extrapolation to sporadic AD. Oligomer biology is still in the theoretical realm, with no clinical validation. APOE support for the amyloid cascade and other inferences from the literature are somewhat circular in their logic. Analogy with amyloidoses might also consider secondary amyloidosis, driven by systemic inflammation and treated by treating the underlying etiology. Much of the remaining literature supporting the amyloid cascade is dominated by hypothesis-generating studies. Importantly, we now have a developing evidence base from controlled clinical trials that can potentially inform the issue of Aβ as a cause or driver of disease in sporadic AD. Emerging data provide clear evidence of target engagement. Clinical outcome, however, has been either marginally positive or similar to placebo. Assuming these findings hold, it appears that Aβ neither drives nor mitigates the disease process.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
This Month in AJP. 本月 AJP。
IF 4.7 2区 医学
American Journal of Pathology Pub Date : 2024-11-10 DOI: 10.1016/j.ajpath.2024.10.012
{"title":"This Month in AJP.","authors":"","doi":"10.1016/j.ajpath.2024.10.012","DOIUrl":"10.1016/j.ajpath.2024.10.012","url":null,"abstract":"","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic, Epigenetic, and Microenvironmental Drivers of Cholangiocarcinoma. 胆管癌的遗传、表观遗传和微环境驱动因素
IF 4.7 2区 医学
American Journal of Pathology Pub Date : 2024-11-10 DOI: 10.1016/j.ajpath.2024.10.013
Vijay Putatunda, Apinya Jusakul, Lewis Roberts, Xin Wei Wang
{"title":"Genetic, Epigenetic, and Microenvironmental Drivers of Cholangiocarcinoma.","authors":"Vijay Putatunda, Apinya Jusakul, Lewis Roberts, Xin Wei Wang","doi":"10.1016/j.ajpath.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.ajpath.2024.10.013","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) is an aggressive and heterogeneous malignancy of the biliary tree that carries a poor prognosis. Multiple features at the genetic, epigenetic, and microenvironmental levels have been identified to better characterize CCA carcinogenesis. Genetic alterations, such as mutations in IDH1/2, BAP1, ARID1A, and FGFR2, play significant roles in CCA pathogenesis, with variations across different subtypes, race/ethnicities, and etiologies. Epigenetic dysregulation, characterized by DNA methylation and histone modifications, further contributes to the complexity of CCA, influencing gene expression and tumor behavior. Furthermore, CCA cells exchange autocrine and paracrine signals with other cancer cells and the infiltrating cell types that populate the microenvironment, including cancer-associated fibroblasts, tumor-associated macrophages, further contributing to an immunosuppressive niche that supports tumorigenesis. This review explores the multifaceted genetic, epigenetic and microenvironmental drivers of CCA. Understanding these diverse mechanisms is essential for characterizing the complex pathways of CCA carcinogenesis and developing targeted therapies to improve patient outcomes.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CORRECTION. 更正。
IF 4.7 2区 医学
American Journal of Pathology Pub Date : 2024-11-07 DOI: 10.1016/j.ajpath.2024.10.009
{"title":"CORRECTION.","authors":"","doi":"10.1016/j.ajpath.2024.10.009","DOIUrl":"10.1016/j.ajpath.2024.10.009","url":null,"abstract":"","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PD-L1 in Melanoma and Extracellular Vesicles Promotes Local and Regional Immune Suppression through M2-like Macrophage Polarization. 黑色素瘤和细胞外囊泡中的 PD-L1 通过 M2 样巨噬细胞极化促进局部和区域免疫抑制。
IF 4.7 2区 医学
American Journal of Pathology Pub Date : 2024-10-29 DOI: 10.1016/j.ajpath.2024.09.011
Lili Huang, Jingbo Yang, Jinjin Zhu, Huaishan Wang, Liyun Dong, Yeye Guo, Yeqing Chen, Feng Zhang, David J Xu, Lingling Ou, Jaiden R Xu, Lei Guan, Quoc D Doan, Andrew Y Fan, Wenqun Zhong, Jina Ko, Chengyu Liang, Meenhard Herlyn, Wei Guo, Xiaowei Xu, Shujing Liu
{"title":"PD-L1 in Melanoma and Extracellular Vesicles Promotes Local and Regional Immune Suppression through M2-like Macrophage Polarization.","authors":"Lili Huang, Jingbo Yang, Jinjin Zhu, Huaishan Wang, Liyun Dong, Yeye Guo, Yeqing Chen, Feng Zhang, David J Xu, Lingling Ou, Jaiden R Xu, Lei Guan, Quoc D Doan, Andrew Y Fan, Wenqun Zhong, Jina Ko, Chengyu Liang, Meenhard Herlyn, Wei Guo, Xiaowei Xu, Shujing Liu","doi":"10.1016/j.ajpath.2024.09.011","DOIUrl":"10.1016/j.ajpath.2024.09.011","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) play dual roles in tumor progression. TAMs are known to induce programmed death ligand-1 (PD-L1) expression in cancer cells. However, the regulatory effects of PD-L1 in melanoma cells on TAM phenotypical switching remain underexplored. Herein, our findings indicated that CD163 and MRC1 levels were significantly elevated in metastatic melanomas compared with primary melanomas, correlating with CD274 expression and predicted patient clinical outcomes. To study the mechanisms regulating M2-like polarization, PD-L1 was knocked out in both YUMM1.7 and B16-F10 melanoma cells. The data revealed that knocking out PD-L1 (PD-L1<sup>KO</sup>) in melanoma resulted in a decelerated in vivo growth rate, accompanied by a significantly increased M1/M2 ratio, more dendritic cells, and enhanced activation of CD8<sup>+</sup> T cells compared with wild-type (WT) melanoma cells. These alterations were associated with decreased expression of M2-associated chemokines (CCL2, CCL3, and CXCL2) and cytokines (IL6, IL10, and TGFβ1). Mice harboring PD-L1<sup>KO</sup> melanomas exhibited elevated levels of CD8<sup>+</sup> T cells in both the tumor-draining lymph nodes and the bloodstream compared with mice with PD-L1<sup>WT</sup> melanomas. Treatment with extracellular vesicles (EVs) derived from PD-L1<sup>KO</sup> melanoma resulted in a reduced tumor growth rate and fewer M2-like macrophages in the tumors compared with EVs from PD-L1<sup>WT</sup> melanomas. Therefore, our data suggest that PD-L1 in melanoma and melanoma-derived EVs induces M2-like polarization, contributing to local and regional immune suppression.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ablation of CD44 Attenuates Adipogenesis in White Adipocytes via the Tryptophan 5-Hydroxylase 2/5-Hydroxytryptamine Axis to Protect Mice from High-Fat Diet-Induced Obesity. 通过 TPH2/5-HT 轴消减 CD44 可减轻白色脂肪细胞的脂肪生成,从而保护小鼠免受高脂饮食诱发的肥胖症。
IF 4.7 2区 医学
American Journal of Pathology Pub Date : 2024-10-29 DOI: 10.1016/j.ajpath.2024.10.005
Yuting Wu, Jinyu Ma, Jing Chen, Xiaoyu Liu, Zhe Wang, Lan Luo, Cheng Sun
{"title":"Ablation of CD44 Attenuates Adipogenesis in White Adipocytes via the Tryptophan 5-Hydroxylase 2/5-Hydroxytryptamine Axis to Protect Mice from High-Fat Diet-Induced Obesity.","authors":"Yuting Wu, Jinyu Ma, Jing Chen, Xiaoyu Liu, Zhe Wang, Lan Luo, Cheng Sun","doi":"10.1016/j.ajpath.2024.10.005","DOIUrl":"10.1016/j.ajpath.2024.10.005","url":null,"abstract":"<p><p>CD44 is a transmembrane protein that plays an essential role in transducing extracellular stimuli into intracellular signaling cascades, especially in cancer cells. Recent studies have shown that CD44 contributes to metabolic regulation. However, the effect of CD44 on adipogenesis in white adipose tissue (WAT) remains unclear. Here, the results showed that the expression of CD44 was largely increased in the inguinal and epididymal WAT of obese mice. Ablation or neutralization of CD44 inhibits adipogenesis in cultured adipocytes. CD44-deficient mice are resistant to high-fat diet-induced obesity and metabolic dysfunction. RNA-sequencing, together with functional studies, revealed that reduced expression of tryptophan 5-hydroxylase 2 (Tph2) in WAT is responsible for the repressed adipogenesis in the absence of CD44. The application of 5-hydroxytryptamine, a product of TPH2, rescues the repressed adipogenesis induced by CD44 neutralization. Moreover, the inhibition of TPH2 by p-chlorophenylalanine recapitulates the beneficial phenotypes observed in CD44-deficient mice. Taken together, these data indicate that CD44 plays a pivotal role in adipogenesis in WAT. In this regard, CD44 and its downstream target TPH2 may hold great therapeutic potential for treating excessive adiposity-related metabolic disorders, such as obesity, insulin resistance, and type 2 diabetes.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sphingosine Kinase 2 Controls the Aggressive Phenotype of Oral Squamous Cell Carcinoma by Regulating miR-205 and miR-296 through p53. 鞘氨醇激酶 2 通过 p53 调节 miR-205 和 miR-296 来控制口腔鳞状细胞癌的侵袭性表型。
IF 4.7 2区 医学
American Journal of Pathology Pub Date : 2024-10-28 DOI: 10.1016/j.ajpath.2024.09.009
Thaís Moré Milan, Gabriel da Silva, Lucas Oliveira Sousa, Andréia Machado Leopoldino
{"title":"Sphingosine Kinase 2 Controls the Aggressive Phenotype of Oral Squamous Cell Carcinoma by Regulating miR-205 and miR-296 through p53.","authors":"Thaís Moré Milan, Gabriel da Silva, Lucas Oliveira Sousa, Andréia Machado Leopoldino","doi":"10.1016/j.ajpath.2024.09.009","DOIUrl":"10.1016/j.ajpath.2024.09.009","url":null,"abstract":"<p><p>Alterations in micro-RNAs, p53, and sphingolipid metabolism have been associated with head and neck squamous cell carcinoma (HNSCC). However, the role of sphingosine kinase (SK)-2, an enzyme crucial for sphingolipid metabolism, is poorly understood in HNSCC. The aim of this study was to investigate how SK2 and p53 interact to regulate miRNAs miR-205 and miR-296. Analysis of small-RNA sequencing data from nontumor oral keratinocytes with SK2 overexpression (NOK-SK2) compared to controls (NOK-Ø) revealed differential expression of >100 miRNAs being half-regulated by p53. The expression of miR-205 was down-regulated, and miR-296 was up-regulated, in NOK-SK2 cells; however, cells with SK2 knockdown and p53 overexpression showed an opposite profile. Proteins involved in miRNA biogenesis were increased in NOK-SK2 cells, while levels were decreased in NOK-SK2 cells with p53 overexpression. Transfection with miR-205 mimic and miR-296 inhibitor decreased the aggressiveness and cancer stem-like cells in oral keratinocytes and oral carcinoma cells with SK2 deregulation. Overexpression of miR-205 in HN12-SK2 cells decreased tumor-formation capacity, and NOK-SK2 cells abrogated tumor growth in mice. The results indicate crosstalk between SK2 and p53 in regulating miRNAs 205 and 296, which could be potential therapeutic targets in the treatment of HNSCC.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ECMTrans-net: Multi-Class Segmentation Network Based on Tumor Tissue in Endometrial Cancer Pathology Images. ECMTrans-net:基于子宫内膜癌病理图像中肿瘤组织的多类分割网络
IF 4.7 2区 医学
American Journal of Pathology Pub Date : 2024-10-28 DOI: 10.1016/j.ajpath.2024.10.008
Tong Yang, Ping Li, Bo Liu, Yuchun Lv, Dage Fan, Yuling Fan, Peizhong Liu, Yaping Ni
{"title":"ECMTrans-net: Multi-Class Segmentation Network Based on Tumor Tissue in Endometrial Cancer Pathology Images.","authors":"Tong Yang, Ping Li, Bo Liu, Yuchun Lv, Dage Fan, Yuling Fan, Peizhong Liu, Yaping Ni","doi":"10.1016/j.ajpath.2024.10.008","DOIUrl":"10.1016/j.ajpath.2024.10.008","url":null,"abstract":"<p><p>Endometrial cancer has the second highest incidence of malignant tumors in the female reproductive system, and accurate and efficient analysis of endometrial cancer pathology images is one of the important research components of computer-aided diagnosis. However, endometrial cancer pathology images have challenges such as smaller solid tumors, lesion areas varying in morphology, and difficulty distinguishing solid and nonsolid tumors, which would affect the accuracy of subsequent pathologic analyses. An Endometrial Cancer Multi-class Transformer Network (ECMTrans-net) is therefore proposed to improve the segmentation accuracy of endometrial cancer pathology images. An ECM-Attention module is first proposed, which can sequentially infer attention maps along three separate dimensions (channel, local spatial, and global spatial) and multiply the attention maps and the input feature map for adaptive feature refinement. This approach would solve the problems of the small size of solid tumors and similar characteristics of solid tumors to nonsolid tumors and further improve the accuracy of segmentation of solid tumors. In addition, an ECM-Transformer module is proposed, which can fuse multi-class feature information and dynamically adjust the receptive field, solving the issue of complex tumor features. Experiments on the Solid Tumor Endometrial Cancer Pathological (ST-ECP) data set found that performances of the ECMTrans-net is superior to state-of-the-art image segmentation methods, and the average values of accuracy, Mean Intersection over Union, precision, and Dice coefficients were 0.952, 0.927, 0.931, and 0.901, respectively.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chronic Coinfection with Pseudomonas aeruginosa and Normal Colony Staphylococcus aureus Causes Lung Structural Damage in the Cystic Fibrosis Rat. 铜绿假单胞菌和正常菌落金黄色葡萄球菌的慢性联合感染会导致囊性纤维化大鼠肺部结构损伤。
IF 4.7 2区 医学
American Journal of Pathology Pub Date : 2024-10-28 DOI: 10.1016/j.ajpath.2024.09.008
Gretchen E Bollar, Johnathan D Keith, Denise D Stanford, Ashley M Oden, S Vamsee Raju, T Spencer Poore, Susan E Birket
{"title":"Chronic Coinfection with Pseudomonas aeruginosa and Normal Colony Staphylococcus aureus Causes Lung Structural Damage in the Cystic Fibrosis Rat.","authors":"Gretchen E Bollar, Johnathan D Keith, Denise D Stanford, Ashley M Oden, S Vamsee Raju, T Spencer Poore, Susan E Birket","doi":"10.1016/j.ajpath.2024.09.008","DOIUrl":"10.1016/j.ajpath.2024.09.008","url":null,"abstract":"<p><p>Cystic fibrosis (CF) respiratory outcomes are heavily influenced by complications of infection. Pseudomonas aeruginosa and Staphylococcus aureus are the most common colonizers of the cystic fibrosis lung, and frequently overlap to cause chronic and persistent coinfections associated with severe disease. However, the dynamics of P. aeruginosa and S. aureus coinfection and its impacts on the development of CF lung structural damage are poorly understood. Additionally, small colony variants (SCVs) of S. aureus have been associated with P. aeruginosa infections in people with CF, but their role in disease progression is largely unknown. In this work, the CF rat was used to model chronic lung coinfection with P. aeruginosa and S. aureus, using clinically and laboratory-derived normal colony and SCV strains of S. aureus to evaluate the impact of phenotype on clinical outcomes. Rats coinfected with clinically derived S. aureus of both phenotypes experienced increased inflammation in the lung, but only the combination of P. aeruginosa and clinically normal colony S. aureus led to lung structural decline, including mucus obstruction and bronchiectasis. In regression analyses, damage was associated with a higher burden of P. aeruginosa, indicating that chronic coinfection with normal colony S. aureus and P. aeruginosa may support the progression CF lung decline driven by P. aeruginosa, which might be avoided when coinfecting S. aureus exhibits the SCV phenotype.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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