Innate Immunity最新文献_第4页

Recognition of Listeria monocytogenes infection by natural killer cells: Towards a complete picture by experimental studies in rats. 自然杀伤细胞对单核增生李斯特菌感染的识别:通过大鼠实验研究获得完整的图像。

IF 3.2 4区医学

Innate Immunity Pub Date : 2023-08-01 DOI: 10.1177/17534259231178223

Hamid Shegarfi

{"title":"Recognition of Listeria monocytogenes infection by natural killer cells: Towards a complete picture by experimental studies in rats.","authors":"Hamid Shegarfi","doi":"10.1177/17534259231178223","DOIUrl":"https://doi.org/10.1177/17534259231178223","url":null,"abstract":"The study of cellular immune responses in animal disease models demands detailed knowledge of development, function, and regulation of immune cells, including natural killer (NK) cells. Listeria monocytogenes (LM) bacterium has been explored in a large area of research fields, including the host pathogen interaction. Although the importance role of NK cells in controlling the first phase of LM burden has been investigated, the interaction between NK cells and infected cells in details are far from being comprehended. From in vivo and in vitro experiments, we can drive several important pieces of knowledge that hopefully contribute to illuminating the intercommunication between LM-infected cells and NK cells. Experimental studies performed in rats revealed that certain NK cell ligands are influenced in LM-infected cells. These ligands include both classical- and non-classical MHC class I molecules and C-type lectin related (Clr) molecules that are ligands for Ly49- and NKR-P1 receptors respectively. Interaction between these receptors:ligands during LM infection, demonstrated stimulation of rat NK cells. Hence, these studies provided additional knowledge to the mechanisms NK cells utilise to recognise and respond to LM infection outlined in the current review.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 6","pages":"110-121"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c8/95/10.1177_17534259231178223.PMC10468624.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10489357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dietary fat differentially modulates the response of bone marrow-derived macrophages to TLR4 and NOD2 agonists. 膳食脂肪可差异性调节骨髓源性巨噬细胞对TLR4和NOD2激动剂的反应。

IF 3.2 4区医学

Innate Immunity Pub Date : 2023-08-01 DOI: 10.1177/17534259231193926

Michael G Shehat, Madelyn H Miller, Ashley N Calder, Timothy A Gilbertson, Justine T Tigno-Aranjuez

{"title":"Dietary fat differentially modulates the response of bone marrow-derived macrophages to TLR4 and NOD2 agonists.","authors":"Michael G Shehat, Madelyn H Miller, Ashley N Calder, Timothy A Gilbertson, Justine T Tigno-Aranjuez","doi":"10.1177/17534259231193926","DOIUrl":"https://doi.org/10.1177/17534259231193926","url":null,"abstract":"Consumption of diets high in fat has been linked to the development of obesity and related metabolic complications. Such associations originate from the enhanced, chronic, low-grade inflammation mediated by macrophages in response to translocated bacteria, bacterial products, or dietary constituents such as fatty acids (FAs). Nucleotide-binding Oligomerization Domain 2 (NOD2) senses muramyl dipeptide (MDP), a component of bacterial peptidoglycan. The inability to sense peptidoglycan through NOD2 has been demonstrated to lead to dysbiosis, increased bacterial translocation, inflammation and metabolic dysfunction. Currently, it is unknown how consumption of HFDs with different FA compositions might influence NOD2-dependent responses. In this study, we subjected WT mice to a control diet or to HFDs comprised of various ratios of unsaturated to saturated fats and determined the macrophage response to TLR4 and NOD2 agonists. A HFD with equal ratios of saturated and unsaturated fats enhanced subsequent responsiveness of macrophages to LPS but not to MDP. However, a high-unsaturated fat diet (HUFD) or a high-saturated fat diet (HSFD) both decreased the responsiveness to NOD2 agonists compared to that observed in control diet (CD) fed mice. These data suggest that dietary fatty acid composition can influence the subsequent macrophage responsiveness to bacterial products.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 6","pages":"122-131"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/55/10.1177_17534259231193926.PMC10468623.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10489899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of neutrophils in different stages of atherosclerosis. 中性粒细胞在动脉粥样硬化不同阶段的作用。

IF 3.2 4区医学

Innate Immunity Pub Date : 2023-08-01 DOI: 10.1177/17534259231189195

Xiaojing Zhang, Zhanfang Kang, Dazhong Yin, Jun Gao

{"title":"Role of neutrophils in different stages of atherosclerosis.","authors":"Xiaojing Zhang, Zhanfang Kang, Dazhong Yin, Jun Gao","doi":"10.1177/17534259231189195","DOIUrl":"https://doi.org/10.1177/17534259231189195","url":null,"abstract":"Neutrophils constitute the first line of defense in human immunity and can be attracted to inflamed and infected sites by various chemokines. As essential players in immune processes, neutrophils theoretically play integral roles in the course of chronic inflammation-induced atherosclerosis. However, because neutrophils are rarely found in atherosclerotic lesions, their involvement in the pathophysiological progression of atherosclerosis has been largely underestimated or ignored. Recent research has revealed convincing evidence showing the presence of neutrophils in atherosclerotic lesions and has revealed neutrophil contributions to different atherosclerosis stages in mice and humans. This review describes the underlying mechanisms of neutrophils in different stages of atherosclerosis and highlights potential neutrophil-targeted therapeutic strategies relevant to atherosclerosis. An in-depth understanding of neutrophils' roles in atherosclerosis pathology will promote exploration of new methods for the prevention and treatment of atherogenesis and atherothrombosis.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 6","pages":"97-109"},"PeriodicalIF":3.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1f/2f/10.1177_17534259231189195.PMC10468622.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10665759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Single cell RNA-sequencing of human precision-cut lung slices: A novel approach to study the effect of vaping and viral infection on lung health. 对人体精密切割肺切片进行单细胞 RNA 测序：研究吸烟和病毒感染对肺部健康影响的新方法。

IF 3.2 4区医学

Innate Immunity Pub Date : 2023-07-01 Epub Date: 2023-06-12 DOI: 10.1177/17534259231181029

Taylor Crue, Grace Yihua Lee, Joyce Yao-Chun Peng, Niccolette Schaunaman, Hina Agraval, Brian J Day, Kris Genelyn Dimasuay, Diana Cervantes, Hamid Nouri, Taylor Nichols, Paige Hartsoe, Mari Numata, Irina Petrache, Hong Wei Chu

{"title":"Single cell RNA-sequencing of human precision-cut lung slices: A novel approach to study the effect of vaping and viral infection on lung health.","authors":"Taylor Crue, Grace Yihua Lee, Joyce Yao-Chun Peng, Niccolette Schaunaman, Hina Agraval, Brian J Day, Kris Genelyn Dimasuay, Diana Cervantes, Hamid Nouri, Taylor Nichols, Paige Hartsoe, Mari Numata, Irina Petrache, Hong Wei Chu","doi":"10.1177/17534259231181029","DOIUrl":"10.1177/17534259231181029","url":null,"abstract":"Vaping is an increasing health threat in the US and worldwide. The damaging impact of vaping on the human distal lung has been highlighted by the recent epidemic of electronic cigarette or vaping use-associated lung injury (EVALI). The pathogenesis of EVALI remains incompletely understood, due to a paucity of models that recapitulate the structural and functional complexity of the human distal lung and the still poorly defined culprit exposures to vaping products and respiratory viral infections. Our aim was to establish the feasibility of using single cell RNA-sequencing (scRNA-seq) technology in human precision-cut lung slices (PCLS) as a more physiologically relevant model to better understand how vaping regulates the antiviral and pro-inflammatory response to influenza A virus infection. Normal healthy donor PCLS were treated with vaping extract and influenza A viruses for scRNA-seq analysis. Vaping extract augmented host antiviral and pro-inflammatory responses in structural cells such as lung epithelial cells and fibroblasts, as well as in immune cells such as macrophages and monocytes. Our findings suggest that human distal lung slice model is useful to study the heterogeneous responses of immune and structural cells under EVALI conditions, such as vaping and respiratory viral infection.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 5","pages":"61-70"},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4e/df/10.1177_17534259231181029.PMC10357887.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9846417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Killer cell immunoglobulin-like receptor (KIR) genes and their HLA ligands in a Brazilian population. 巴西人群中的杀伤细胞免疫球蛋白样受体(KIR)基因及其HLA配体

IF 3.2 4区医学

Innate Immunity Pub Date : 2023-07-01 DOI: 10.1177/17534259231178592

Daniela Maira Cardozo, Amanda Vansan Marangon, Fernando Guimarães, Silvia Marques, Sofia Lieber, Márcia Delamain, Francisco Aranha, Jeane Eliete Laguila Visentainer, Cármino Antonio de Souza

{"title":"Killer cell immunoglobulin-like receptor (KIR) genes and their HLA ligands in a Brazilian population.","authors":"Daniela Maira Cardozo, Amanda Vansan Marangon, Fernando Guimarães, Silvia Marques, Sofia Lieber, Márcia Delamain, Francisco Aranha, Jeane Eliete Laguila Visentainer, Cármino Antonio de Souza","doi":"10.1177/17534259231178592","DOIUrl":"https://doi.org/10.1177/17534259231178592","url":null,"abstract":"Killer cell immunoglobulin-like receptors (KIR) exhibit extensive diversity, giving rise to different KIR profiles in populations worldwide. This study aimed to investigate the distribution of KIR genes and HLA ligands in a population from Campinas, southeastern Brazil (n = 292), and to compare their results with other populations. A comprehensive analysis of population-specific genes, genotype, and haplotype frequencies of KIR may facilitate a better understanding of their evolution and role in immunity. The genotyping of 16 KIR genes and HLA class I alleles was performed by the reverse sequence-specific oligonucleotide methodology using the Luminex platform (One Lambda, Inc., Canoga Park, CA). The framework genes were present in all individuals, with the most common non-framework KIR genes detected being KIR2DP1(96.6%), KIR2DL1(95.5%), KIR3DL1(94.5%), KIR2DS4(93.8%) and KIR2DL3(87.3%). KIR2DS1, KIR2DS3, KIR2DS5, and KIR3DS1 presented frequencies below 40%. KIR2DL2, KIR2DL5, and KIR2DS2 showed intermediate frequencies (between53% and 58%). The activating gene KIR2DS5 was the least common in this population (30.8%). Forty-five KIR profiles were found with the commonest being the homozygous A haplotype (27.4%). The distribution of KIR genes in the Brazilian population is similar to Caucasian European and Euro-descendant populations.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 5","pages":"71-82"},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/82/6f/10.1177_17534259231178592.PMC10357888.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9903303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association between interleukin-27 gene polymorphisms and Plasmodium falciparum Malaria. 白细胞介素-27基因多态性与恶性疟原虫疟疾的关系

IF 3.2 4区医学

Innate Immunity Pub Date : 2023-07-01 DOI: 10.1177/17534259231178594

Nada H Aljarba, Mashael R Al-Anazi, Tahani M Al-Hazani, Mohammed I Shafeai, Fuad H Rudiny, Ali M Motaen, Saad M Bin Dajem, Hani Alothaid, Jahad Alghamdi, Saad Alkahtani, Ahmed A Al-Qahtani

{"title":"Association between interleukin-27 gene polymorphisms and Plasmodium falciparum Malaria.","authors":"Nada H Aljarba, Mashael R Al-Anazi, Tahani M Al-Hazani, Mohammed I Shafeai, Fuad H Rudiny, Ali M Motaen, Saad M Bin Dajem, Hani Alothaid, Jahad Alghamdi, Saad Alkahtani, Ahmed A Al-Qahtani","doi":"10.1177/17534259231178594","DOIUrl":"https://doi.org/10.1177/17534259231178594","url":null,"abstract":"Malaria is often characterized by a complicated disease course due to multifaceted intrinsic genetic factors of the host and the parasite. This study aimed to investigate the role of interleukin-27 (IL-27) gene polymorphisms in Plasmodium falciparum malaria infection in a Saudi Arabian cohort. This case-control study obtained blood samples from 250 malaria patients with P. falciparum and 200 randomly identified healthy control subjects from the Malaria Center in the Jazan area. Malaria patients were grouped into three cohorts as follow: low (<500 parasites/µl of blood), moderate (500-1000 parasites/µl of blood), and high (>1000 parasites/µl of blood) parasitemia. The results show that the IL-27 variant rs181209 was significantly associated with malaria patients (P = 0.026). Similarly, the homozygous GG genotype of rs26528 was also associated with risk of developing P. falciparum malaria (P = 0.032). The minor allele C of variant rs181206 exhibited an association with low to moderate parasitemia (P = 0.046). Furthermore, the rs181209 AA genotype was statistically significant in age group 1-5 years (P = 0.049). In conclusion, this study suggests that variant rs181209 and rs26528 could be associated with the risk of malaria infection by P. falciparum in the population studied.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 5","pages":"83-94"},"PeriodicalIF":3.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c4/c3/10.1177_17534259231178594.PMC10357889.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9846415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A TLR4 agonist liposome formulation effectively stimulates innate immunity and enhances protection from bacterial infection. TLR4激动剂脂质体制剂可有效刺激先天免疫，增强对细菌感染的保护。

IF 3.2 4区医学

Innate Immunity Pub Date : 2023-04-01 DOI: 10.1177/17534259231168725

Jodi F Hedges, Deann T Snyder, Amanda Robison, Macy A Thompson, Klara Aspelin, Jack Plewa, Jory Baldridge, Mark A Jutila

{"title":"A TLR4 agonist liposome formulation effectively stimulates innate immunity and enhances protection from bacterial infection.","authors":"Jodi F Hedges, Deann T Snyder, Amanda Robison, Macy A Thompson, Klara Aspelin, Jack Plewa, Jory Baldridge, Mark A Jutila","doi":"10.1177/17534259231168725","DOIUrl":"https://doi.org/10.1177/17534259231168725","url":null,"abstract":"Stimulation of innate immunity can protect against infectious insult and could be used in combination with other therapies. Since antibiotic resistance is an increasing concern, strategies to reduce the dose or eliminate the need for these drugs are warranted. Lipo-CRX is a formulation in which the TLR4 agonist CRX-527 is incorporated into lipid membranes in liposomes. Lipo-CRX is less inflammatory than either CRX-527 or LPS, but retains unique capacity to enhance host defense responses. We compared lipo-CRX to other agonists in vitro using mammalian cells and in vivo in mice, and assessed indicators of innate immune responses and protection from bacterial infection. Lipo-CRX is similar to E. coli LPS in its capacity to activate bovine γδ T cells and to recruit neutrophils into mouse lungs, but with less reactivity in the LAL assay. However, lipo-CRX uniquely induced the production of systemic innate immune cytokines. In the mouse model of brucellosis, delivery of lipo-CRX to the lungs reduced the dissemination of B. abortus. While lipo-CRX or the antibiotic ampicillin alone did not alter B. abortus burdens in the lung, the combination had a synergistic beneficial effect. Our data suggest that stimulating the innate immune system with lipo-CRX, either alone or when combined with antibiotics, can enhance bacterial clearance in the mouse model of brucellosis.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 3-4","pages":"45-57"},"PeriodicalIF":3.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/20/10.1177_17534259231168725.PMC10331211.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9772012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Increased circulating monocyte MDSCs positively correlate with serum Interleukin-10 in metastatic melanoma patients. 在转移性黑色素瘤患者中，循环单核细胞MDSCs增加与血清白细胞介素-10呈正相关。

IF 3.2 4区医学

Innate Immunity Pub Date : 2023-04-01 DOI: 10.1177/17534259231172079

Katarina Mirjačić Martinović, Ana Vuletić, Nevena Tišma Miletić, Milica Nedeljković, Nada Babović, Suzana Matković, Vladimir Jurišić

{"title":"Increased circulating monocyte MDSCs positively correlate with serum Interleukin-10 in metastatic melanoma patients.","authors":"Katarina Mirjačić Martinović, Ana Vuletić, Nevena Tišma Miletić, Milica Nedeljković, Nada Babović, Suzana Matković, Vladimir Jurišić","doi":"10.1177/17534259231172079","DOIUrl":"https://doi.org/10.1177/17534259231172079","url":null,"abstract":"Numerous immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and inhibitory cytokines identified in melanoma microenvironment have the important role in immune escape. Therefore, in this study we analyzed monocytic (m)MDSCs in peripheral blood of metastatic melanoma (MM) patients. In peripheral blood of 35 MM patients and 30 healthy controls we analyzed percentage of CD14 + HLA-DR- mMDSCs in monocyte gate and the mean fluorescence intensity of Foxp3 in CD25 + CD4 + regulatory T cells by Flow cytometry. Serum levels of transforming growth factor beta, interferon-gamma, interleukin (IL)-6, IL-8, IL-10 are measured by ELISA assays. In this study MM patients have significantly higher percentage of CD14 + HLA-DR- mMDSCs, as well as increased the baseline mMDSC/PBMC subset (NK, T, B cells, monocytes) ratio. Although there is no significant difference in the percentage of mMDSCs between groups of MM patients with different localization of distant metastasis, patients with elevated serum lactate dehydrogenase (LDH) have statistically significant higher percentage of these cells compared to LDH negative patients. Furthermore, in MM patients there is statistically significant positive correlation between values of IL-10 and the percentage of mMDSCs, only. Therefore, therapeutics that target circulating mMDSCs and IL-10 may have a big importance in the improvement of antitumor immunity in MM patients.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 3-4","pages":"37-44"},"PeriodicalIF":3.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c8/17/10.1177_17534259231172079.PMC10331212.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9825492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis and validation of click-modified NOD1/2 agonists 点击修饰NOD1/2激动剂的合成与验证

IF 3.2 4区医学

Innate Immunity Pub Date : 2023-03-28 DOI: 10.1101/2023.03.28.534546

R. Bharadwaj, Madison V. Anonick, S. Mashayekh, Ashley R. Brown, Kimberly A. Wodzanowski, K. Okuda, N. Silverman, C. Grimes

引用次数: 1

C/EBPβ deficiency enhances the keratinocyte innate immune response to direct activators of cytosolic pattern recognition receptors. C/EBPβ 缺乏会增强角质形成细胞对细胞膜模式识别受体直接激活剂的先天性免疫反应。

IF 3.2 4区医学

Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-04-24 DOI: 10.1177/17534259231162192

John S House, Sophia Gray, Jennifer R Owen, Dereje D Jima, Robert C Smart, Jonathan R Hall

{"title":"C/EBPβ deficiency enhances the keratinocyte innate immune response to direct activators of cytosolic pattern recognition receptors.","authors":"John S House, Sophia Gray, Jennifer R Owen, Dereje D Jima, Robert C Smart, Jonathan R Hall","doi":"10.1177/17534259231162192","DOIUrl":"10.1177/17534259231162192","url":null,"abstract":"The skin is the first line of defense to cutaneous microbes and viruses, and epidermal keratinocytes play a critical role in preventing infection by viruses and pathogens through activation of the type I interferon (IFN) response. Using RNAseq analysis, here we report that the conditional deletion of C/EBPβ transcription factor in mouse epidermis (CKOβ mice) resulted in the upregulation of IFNβ and numerous keratinocyte interferon-stimulated genes (ISGs). The expression of cytosolic pattern recognition receptors (cPRRs), that recognize viral RNA and DNA, were significantly increased, and enriched in the RNAseq data set. cPRRs stimulate a type I IFN response that can trigger cell death to eliminate infected cells. To determine if the observed increases in cPRRs had functional consequences, we transfected CKOβ primary keratinocytes with the pathogen and viral mimics poly(I:C) (dsRNA) or poly(dA:dT) (synthetic B-DNA) that directly activate PRRs. Transfected CKOβ primary keratinocytes displayed an amplified type I IFN response which was accompanied by increased activation of IRF3, enhanced ISG expression, enhanced activation of caspase-8, caspase-3 and increased apoptosis. Our results identify C/EBPβ as a critical repressor of the keratinocyte type I IFN response, and demonstrates that the loss of C/EBPβ primes keratinocytes to the activation of cytosolic PRRs by pathogen RNA and DNA to induce cell death mediated by caspase-8 and caspase-3.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"29 1-2","pages":"14-24"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/75/28/10.1177_17534259231162192.PMC10164275.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9438653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0