Innate ImmunityPub Date : 2025-01-01Epub Date: 2025-08-21DOI: 10.1177/17534259251360484
Viviane Filor, Joanna Myslinska, Amitis Saliani, Jesmond Dalli, Peter Olinga, Wolfgang Bäumer, Dirk Werling
{"title":"Pre-stimulation of precision-cut bovine udder slices with zymosan before LPS exposure indicates aspects of trained immunity especially in the absence of FCS.","authors":"Viviane Filor, Joanna Myslinska, Amitis Saliani, Jesmond Dalli, Peter Olinga, Wolfgang Bäumer, Dirk Werling","doi":"10.1177/17534259251360484","DOIUrl":"10.1177/17534259251360484","url":null,"abstract":"<p><p>Mastitis in cattle poses a significant health challenge and results in substantial economic losses for the dairy industry. This study aimed to extend the existing precision-cut bovine udder slices (PCBUS) model as an <i>in vitro</i> model to explore the potential of inducing trained immunity in the udder with the goal to use the resulting knowledge for potential new treatment strategies. Interestingly, incubation of PCBUS with 10% fetal calf serum (FCS), but no 2% or FCS-free, negatively affected the production of some of the chemokines/cytokines analysed. When trained immunity was induced by zymosan, followed by stimulation with <i>E. coli</i>-derived lipopolysaccharide (LPS), production of interleukin (IL)-1β, IL-6, tumor necrosis factor α and interferon (IFNγ) was downregulated while production of IL-17A and pro-resolving lipid mediators (leukotrienes and prostaglandins) was upregulated. While the current experimental setup did not definitively confirm the induction of trained immunity for all parameters analysed in PCBUS, it validated the utility of PCBUS as a robust <i>in vitro</i> model for studying bovine udder inflammation. This model offers a promising platform for developing innovative mastitis treatments, particularly given the growing concern over antimicrobial resistance, as well as offering alternatives to the use of live animals in experimental studies in line with the 3Rs principles. It also provides a valuable tool for advancing our understanding of immune responses in the bovine udder. By adapting the precision-cut tissue slice technique to bovine udders, this model enables extensive research into new therapeutic approaches and supports basic research efforts to characterise complex pathophysiological processes associated with mastitis. Furthermore, our data highlight the potential limitations of FCS in <i>in vitro</i> studies. Our data should not only stimulate the discussion about FCS in homologues or heterologues species, but should also be kept in mind regarding the need for foetal calves to generate FCS in line with the 3Rs guideline.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251360484"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953035","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}
Innate ImmunityPub Date : 2025-01-01Epub Date: 2025-06-30DOI: 10.1177/17534259251355029
Budjav Jadamba, Jihye Park, Heedoo Lee
{"title":"Biological significance of extracellular vesicles in innate immune system.","authors":"Budjav Jadamba, Jihye Park, Heedoo Lee","doi":"10.1177/17534259251355029","DOIUrl":"10.1177/17534259251355029","url":null,"abstract":"<p><p>Extracellular vesicles (EVs), which are nanosized membranous structures released by diverse cell types, serve as crucial mediators of intercellular communication. Recent evidence has highlighted the dynamic transfer of various biological components, including proteins, lipids, mRNAs, non-coding RNAs, miRNAs, and DNA, via EVs. Immuno-stimulated cells actively release EVs that play a pivotal role in regulating the innate immune system. This study comprehensively reviews the current scientific findings, shedding light on the intricate biological roles of EVs in regulating innate immune cells and the overall immune system. This discussion encompasses diverse pathophysiological conditions and provides valuable insights into the multifaceted contributions of EVs to innate immune responses.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251355029"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527820","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}
{"title":"Effect of <i>Cardamine violifolia</i> on muscle protein degradation and anti-oxidative capacity in weaned piglets after Lipopolysaccharide challenge.","authors":"Nianbang Wu, Shunkang Li, Yanling Kuang, Wensheng He, Huiling Zhu, Qingyu Gao, Liping Liu, Shuiyuan Cheng, Yulan Liu, Xin Cong, Dan Wang","doi":"10.1177/17534259251322589","DOIUrl":"10.1177/17534259251322589","url":null,"abstract":"<p><p>This study aimed to investigate the impact of <i>Cardamine violifolia</i> on muscle protein degradation, the inflammatory response and antioxidant function in weaned piglets following LPS challenge. Twenty-four weaned piglets were used in a 2 × 2 factorial experiment with dietary treatment (sodium selenite or <i>Cardamine violifolia</i>) and LPS challenge. After 28 days of feeding, pigs were injected intraperitoneally with 100 μg/kg LPS or saline. Dietary supplementation with <i>Cardamine violifolia</i> mitigated the reduction in insulin and growth hormone levels induced by LPS. It also curbed the LPS-induced elevation of plasma glucagon, urea nitrogen, and creatinine concentrations. <i>Cardamine violifolia</i> reduced muscle damage caused by LPS, as evidenced by increased protein content and protein/DNA ratio and decreased TNF-α and IL-1β mRNA expression. Furthermore, <i>Cardamine violifolia</i> modulated the expression of FOXO1, FOXO4, and MuRF1 in muscle, indicative of the protective effect against muscle protein degradation. Enhanced muscle antioxidant function was observed in the form of increased T-AOC, reduced MDA concentration, and decreased mRNA expression of GPX3, DIO3, TXNRD1, SELENOS, SELENOI, SELENOO, and SEPHS2 in LPS-treated piglets. The findings suggest that <i>Cardamine violifolia</i> supplementation can effectively alleviate muscle protein degradation induced by LPS and enhance the antioxidant capacity in piglets.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251322589"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448993","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}
Innate ImmunityPub Date : 2025-01-01Epub Date: 2025-08-18DOI: 10.1177/17534259251367263
Ella L Brunsting, Darren J Perkins
{"title":"Working in negative space: Type I interferon mediated immuno-modulation through transcriptional suppression in disease and homeostasis.","authors":"Ella L Brunsting, Darren J Perkins","doi":"10.1177/17534259251367263","DOIUrl":"10.1177/17534259251367263","url":null,"abstract":"<p><p>The type I interferon family of cytokines are rapidly produced following innate pattern recognition receptor engagement and establish a critical early state of host defense. Type I interferons act in antiviral immunity as transcriptional activators and the binding of any type I interferon to the common IFNAR receptor triggers the transcription of <u>I</u>nterferon <u>S</u>timulated <u>G</u>enes (ISGs). A defined set of ISGs have been described through exhaustive studies and the protein products of these ISGs function to increase cell intrinsic resistance to viral growth and to promote viral clearance. Simultaneously, interferons also drive a much less well studied program of transcriptional suppression, inhibiting the expression of an unknown number of genes, with poorly understood consequences for disease. The limited number of genes currently known to be transcriptionally suppressed by IFN are enriched for those with immune-mediating activities such as inflammatory cytokines (e.g., IL-1β), cytokine receptors (e.g., IFNγR) and chemokines. Interferon dependent transcriptional suppression of immune response genes is therefore thought to underlie the immune suppression associated with interferon production during many bacterial infections (e.g., mycobacterium tuberculosis and listeria monocytogenes) and may also explain the palliative effects of interferons in some autoimmune diseases. Despite the health relevance of IFN driven transcriptional suppression, no consensus molecular model exists to explain its selectivity or regulation. In this review we highlight the current literature detailing the known targets of IFN transcriptional suppression within the various disease models in which it has been observed. We also review the relevant molecular mechanisms which have been proposed to explain transcriptional suppression by interferons and discuss the remaining open questions in this field with an ambition to stimulate future work in this area.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251367263"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873064","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}
Innate ImmunityPub Date : 2025-01-01Epub Date: 2025-10-30DOI: 10.1177/17534259251392993
Mahjabin Sanam, Chowdhury Fatema Tuz Zohra Hossain, Tahmida Binte Hyder, Reasat Tarannum, Jahin Fairuj Oishi, Kazi Md Mostafizur Rahman, Sm Bakhtiar Ul Islam, Nayeema Bulbul, Jinath Sultana Jime, Md Asaduzzaman Shishir, Ashrafus Safa, Md Fakruddin
{"title":"Bridging two worlds: Host Microbiota crosstalk in health and dysregulation.","authors":"Mahjabin Sanam, Chowdhury Fatema Tuz Zohra Hossain, Tahmida Binte Hyder, Reasat Tarannum, Jahin Fairuj Oishi, Kazi Md Mostafizur Rahman, Sm Bakhtiar Ul Islam, Nayeema Bulbul, Jinath Sultana Jime, Md Asaduzzaman Shishir, Ashrafus Safa, Md Fakruddin","doi":"10.1177/17534259251392993","DOIUrl":"10.1177/17534259251392993","url":null,"abstract":"<p><p>The gut microbiota plays a crucial role in various physiological functions, such as the production of microbial compounds and maintaining homeostatic equilibrium by complex host-microbial interactions. However, any shift in the constitution and diversity of the microbiota or abnormal interaction with the host can prompt the development of dysbiosis. This review thus illustrates that microbial metabolites, notably short-chain fatty acids, tryptophan metabolites, bile acids, and polyamines, exert significant regulatory effects on innate and adaptive immunological processes, immune response and intestinal barrier integrity through specific receptor activation, involving TLRs, NODs, GPCRs, nuclear receptors, and Wnt/β-catenin. It further explores the disruption of host signalling pathways, caused by dysbiosis, promoting the transcription of specific genes and activating pro-inflammatory pathways. Consequently, this suggests that microbiota acts beyond general health, eventually contributing to gastrointestinal, metabolic, and neurological disorders. Lastly, this review highlights therapeutic approaches required to restore balance and uphold physiological balance.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251392993"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12576186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408997","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}
{"title":"The effect of chemical fixation with paraformaldehyde, glutardialdehyde or methanol on immunofluorescence staining of neutrophils and neutrophil extracellular traps.","authors":"Veronika Pilchová, Armina Richter, Marita Meurer, Claudia Schulz, Maren von Köckritz-Blickwede","doi":"10.1177/17534259241307563","DOIUrl":"10.1177/17534259241307563","url":null,"abstract":"<p><p>The formation of neutrophil extracellular traps (NETs) is known as an important part of the innate immune response. Still, some mechanisms regarding their formation and role during a disease are not completely understood yet. To visualize NETs by immunofluorescence microscopy, a chemical fixation is required. Therefore, this study focused on the effect of chemical fixatives on immunofluorescence staining of selected neutrophil and NET-markers, including myeloperoxidase (MPO), DNA/histone-1-complexes and citrullinated histone H3 (H3cit). Neutrophils isolated from fresh human blood were stimulated with phorbol-12-myristate 13-acetate (PMA) to induce NETs and fixed with paraformaldehyde (PFA, 4%), glutardialdehyde (GA, 5%) or methanol (MeOH, 100%) using different incubation times depending on the used fixative. We found that different fixation times with PFA had no effect on the staining intensity of MPO or DNA/histone-1-complex antibodies. For the staining of H3cit, fixation with PFA for 24 h decreased the signal intensity whereas 30 min fixation time had no effect. In contrast, glutardialdehyde induced a high amount of autofluorescence, and the fixation with 100% MeOH resulted in visible cellular damage. Therefore, we recommend 15-30 min PFA fixation for the respective stainings. Our results provide a solid basis for future experiments to study neutrophil activation and NET-formation.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259241307563"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448968","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}
Innate ImmunityPub Date : 2025-01-01Epub Date: 2025-05-23DOI: 10.1177/17534259251341659
Jirapat Jaisue, Naoki Suzuki, Takahiro Nii, Naoki Isobe
{"title":"Mammary leukocytes function of endotoxin tolerant goat induced by intrauterine infusion of lipopolysaccharide.","authors":"Jirapat Jaisue, Naoki Suzuki, Takahiro Nii, Naoki Isobe","doi":"10.1177/17534259251341659","DOIUrl":"10.1177/17534259251341659","url":null,"abstract":"<p><p>A previous study found that repeated intrauterine infusions of lipopolysaccharide (LPS) followed by an LPS infusion into the mammary glands attenuated the mammary inflammatory response. This suggests that repeated LPS infusion into the uterus promotes endotoxin tolerance (ET) in the mammary gland. However, the specific changes in mammary glands under ET conditions remain unclear. We hypothesized that ET affects leukocyte function in milk. This study aimed to investigate leukocyte function in milk under ET conditions induced through repeated LPS infusions into the uterus for three days followed by LPS infusion into the mammary glands of goats. Goats in the IU group (n = 17) received an infusion of 100 μg LPS in 5 ml saline into the uterus for three consecutive days (d -3, -2, and -1), whereas the goats in the control group did not receive this infusion (n = 19). On d 0, 1 μg LPS in 5 ml saline was infused into the mammary glands of both groups. Milk was collected 0, 4, 8, 12, 24, 48, 72, and 120 h after LPS intramammary infusion. The IU group decreased cytokine production (interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-1Ra) in milk following intramammary LPS infusion. Moreover, leukocyte activation, measured by phagocytic activity and CD11b expression, was higher in the IU group than in the control group. These findings suggest that goats exhibit enhanced leukocyte function in mammary glands under ET conditions, induced by repeated intrauterine infusion of LPS.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251341659"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127426","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}
Innate ImmunityPub Date : 2025-01-01Epub Date: 2025-11-14DOI: 10.1177/17534259251394124
Filip Lewandowski, Rafał Hrynkiewicz, Karolina Wiśniewska, Karolina Pierzynowska, Paulina Niedźwiedzka-Rystwej
{"title":"Primer investigation of RIG-I-like receptors expression in virus infection with the acute character.","authors":"Filip Lewandowski, Rafał Hrynkiewicz, Karolina Wiśniewska, Karolina Pierzynowska, Paulina Niedźwiedzka-Rystwej","doi":"10.1177/17534259251394124","DOIUrl":"10.1177/17534259251394124","url":null,"abstract":"<p><p>This study investigates the expression of RIG-I-like receptors (RLRs) - RIG-I, MDA5, and LGP2 - in <i>Lagovirus europaeus</i>/GI.2 infections causing Rabbit Hemorrhagic Disease. Despite over 30 years of study, the acute pathogenesis remains incompletely understood. Lack of in vitro culture systems hampers vaccine development. The experiment, conducted on European rabbits, reveals a significant increase in RLR expression during infection, particularly in organs associated with severe pathology. The findings suggest a pivotal role for RLRs, especially RIG-I, in the host's defense against <i>Lagovirus europaeus</i>. Further research is needed to unravel the complete molecular pathway and associated factors, offering potential insights for therapeutic interventions.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251394124"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12618830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523427","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}
Innate ImmunityPub Date : 2024-12-23DOI: 10.1177/17534259241306237
Hee Young Cho, Kyo Hoon Park, Eunji Oh, Min Jung Lee, Bo Young Choi, Eun Mi Im
{"title":"Plasma acute phase proteins as potential predictors of intra-amniotic inflammation and infection in preterm premature rupture of membranes.","authors":"Hee Young Cho, Kyo Hoon Park, Eunji Oh, Min Jung Lee, Bo Young Choi, Eun Mi Im","doi":"10.1177/17534259241306237","DOIUrl":"10.1177/17534259241306237","url":null,"abstract":"<p><strong>Background: </strong>We aimed to investigate the potential of altered levels of various acute phase proteins (APPs) in the plasma, either used alone or in combination with ultrasound-, clinical-, and conventional blood-based tests, for predicting the risk of intra-amniotic inflammation (IAI), microbial invasion of the amniotic cavity (MIAC), histologic chorioamnionitis (HCA), and funisitis in women with preterm premature rupture of membranes (PPROM).</p><p><strong>Methods: </strong>A total of 195 consecutive pregnancies involving singleton women with PPROM (at 23 + 0-34 + 0 weeks) who underwent amniocentesis and from whom plasma samples were obtained at amniocentesis were retrospectively included in this study. Amniotic fluid (AF) was cultured to assess the MIAC and analyzed for interleukin (IL)-6 levels to define IAI (AF IL-6 level of ≥2.6 ng/mL). The plasma concentrations of hepcidin, mannose-binding lectin (MBL), pentraxin-2, retinol-binding protein 4 (RBP4), serum amyloid A1 (SAA1), and serpin A1 were determined using ELISA. Ultrasonographic cervical length (CL), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein levels were measured. IAI/MIAC was defined as IAI, MIAC, or both.</p><p><strong>Results: </strong>Multivariate logistic regression analyses showed the following: (1) elevated plasma levels of hepcidin and SAA1 and decreased levels of RBP4 in the plasma were independently associated with IAI/MIAC and (2) decreased plasma RBP4 levels were independently associated with funisitis; however, (3) none of the plasma APPs investigated were associated with acute HCA when adjusted for baseline covariates. Using stepwise regression analysis, noninvasive prediction models comprising plasma RBP4 levels, CL, NLR, and gestational age at sampling were proposed, which provided a good prediction of IAI/MIAC and funisitis (area under the curve: 0.80 and 0.72, respectively).</p><p><strong>Conclusions: </strong>Hepcidin, RBP4, and SAA1 were identified as potential APP biomarkers in the plasma predictive of IAI/MIAC or funisitis in patients with PPROM. In particular, combination of these APP biomarkers with ultrasound-, clinical-, and conventional blood-based markers can significantly support the diagnosis of IAI/MIAC and funisitis.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":" ","pages":"17534259241306237"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876977","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}