Innate Immunity最新文献

{"title":"Preclinical development of the TLR4 antagonist FP12 as a drug lead targeting the HMGB1/MD-2/TLR4 axis in lethal influenza infection.","authors":"Kari Ann Shirey, Alessio Romerio, Mohammed Monsoor Shaik, David S Leake, Charys Palmer, Natalia Skupinska, Jules Paton, Grisha Pirianov, Jorge Cg Blanco, Stefanie N Vogel, Francesco Peri","doi":"10.1177/17534259241313201","DOIUrl":"10.1177/17534259241313201","url":null,"abstract":"<p><strong>Background: </strong>Acute Lung Injuries (ALI) are a severe consequence of influenza-induced cytokine storm that can cause respiratory failure and death. It has been demonstrated that Toll-like Receptor 4 (TLR4) is involved in cytokine storm and that TLR4^-/- mice are protected against ALI. Therefore, TLR4 is a prime target for protection against ALI. FP12 is a known TLR4 antagonist that reduces TLR4-dependent immune activation and it is a promising lead compound for the treatment of innate immunity related pathologies.</p><p><strong>Objectives: </strong>We present here the preclinical development of FP12 as an anti-inflammatory lead compound acting on influenza-induced ALI.</p><p><strong>Methods: </strong><i>In vitro:</i> We pre-treated THP-1 cells with FP12 (10 μM) for 0.5 h, then exposed to LPS (100 ng/ml) for 0 to 16 h. In some experiments, cells were simultaneously incubated with FP12 and LPS, or FP12 was added 30 min after LPS. Cytokine levels were measured by Western blot and ELISA assays. <i>In vivo:</i> WT C57BL/6J mice were infected with mouse-adapted influenza virus (PR8). Two days after infection, mice received either vehicle, FP7 (200 µg/mouse), or FP12 (200 µg/mouse) once daily (Day 2 to Day 6). Mice were monitored daily for survival for 14 days. Data were collected through histological staining, qRT-PCR, and ELISA assay.</p><p><strong>Results: </strong>FP12 treatment inhibited both LPS- and HMGB1-induced TLR4 intracellular pathways (MyD88 and TRIF) leading to significantly reduced levels of a variety of proinflammatory cytokines including Type I interferon (IFN-β), highlighting its effectiveness in controlling proinflammatory protein production and reducing inflammation. FP12 protected mice therapeutically from influenza virus-induced lethality and reduced both cytokine gene expression and High Mobility Group Box 1 (HMGB1) levels in the lungs as well as ALI.</p><p><strong>Conclusion: </strong>FP12 can antagonize TLR4 activation in vitro and protects mice from severe influenza infection, most likely by reducing the TLR4-dependent cytokine storm mediated by danger-associated molecular patterns (DAMPs).</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259241313201"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541972","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":"Inherent immunity and adaptive immunity: Mechanism and role in AECOPD.","authors":"Linguangjin Wu, Erxin Zhang, Yadan Tu, Yong Chen, Chenghu Wang, Yi Ren, Bangjiang Fang","doi":"10.1177/17534259251322612","DOIUrl":"10.1177/17534259251322612","url":null,"abstract":"<p><p>Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the leading cause of hospitalization and mortality in COPD patients. The occurrence of antibiotic resistance and the progression of non-infectious diseases contribute to poor patient outcomes. Thus, a comprehensive understanding of the mechanisms underlying AECOPD is essential for effective prevention. It is widely acknowledged that the immune system plays a fundamental role in pathogen clearance and the development of inflammation. Immune dysregulation, either due to deficiency or hyperactivity, has been implicated in AECOPD pathogenesis. Therefore, the purpose of this review is to investigate the possible mechanisms underlying dysregulated immune function and disease progression in COPD patients, specifically focusing on the innate and adaptive immune responses. The ultimate aim is to provide new insights for clinical prevention and treatment strategies targeting AECOPD.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251322612"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523370","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 imbalance of circulating PD-L1-expressing non-classical/ classical monocytes is involved in immunocompromised host related pulmonary opportunistic infection.","authors":"Danhong Zhou, Yujia Jin, Yifan Jin, Yu Shen, Qiuxia Qu, Cheng Chen","doi":"10.1177/17534259251316152","DOIUrl":"10.1177/17534259251316152","url":null,"abstract":"<p><p>The application of biological therapy and glucocorticoids in Auto-immune diseases (AID) patients will cause immunocompromised host (ICH) prone to infection. And monocytes play a key role in both innate and adaptive immune responses. We aimed to investigate the changes of circulating monocyte subsets in AID or AID-ICH patients with pulmonary infection. The subgroups and PD-L1 expression of monocytes were measured by flow cytometry in healthy individuals (HC), new-onset AID patients (AID cohort) and AID-ICH patients with pulmonary opportunistic infection (AID-ICH cohort). Flow cytometry analysis was used to determine the distribution of monocyte subsets, including classical monocytes (CL, CD14⁺⁺CD16^-), intermediate monocytes (ITM, CD14⁺⁺CD16⁺) and non-classical monocytes (NC, CD14^+/-CD16⁺⁺), as well as the dynamic change of PD-L1 ⁺cluster among monocyte subsets. Among total monocyte, AID-ICH displayed decreased CL subset along with increased NC subset compared to HCs and AID. Regarding PD-L1 ⁺monocytes, although CL subset constituted the majority of that in HCs, AIDs and AID-ICHs, imbalance of NC/CL within PD-L1 ⁺monocytes was only noticed in AID-ICHs (<i>P</i> < 0.05). Furthermore, when AID subjects were developed into immunocompromised status (ICH), PD-L1 ⁺cluster in CL was minorly decreased (<i>P</i> > 0.05). Clinically, the lower ratio of PD-L1 ⁺cluster among CL subset (<i>P</i> < 0.05) and the less differentiated CL in PD-L1 ⁺monocytes (<i>P</i> < 0.05) was more likely to leaded to disease progression. The imbalance of circulating NC/CL subset was remarkable in immunocompromised host with pulmonary opportunistic infection, especially involvement of PD-L1⁺ cluster, which served as a potential biomarker in clinical practice.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251316152"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023329","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":"Association of killer immunoglobulin-like receptor genotypes and haplotypes with acute lymphoblastic leukemia risk.","authors":"Jameel Al-Tamimi, Suliman Alomar, Ali Aljuaimlani, Lamjed Mansour","doi":"10.1177/17534259251314774","DOIUrl":"10.1177/17534259251314774","url":null,"abstract":"<p><strong>Background: </strong>Killer immunoglobulin-like receptors (KIRs) are key molecules used by natural killer (NK) cells to interact with target cells. These receptors exhibit extensive genotypic polymorphism which has been associated with varying outcomes in immune responses against diseases. This study aimed to investigate the relationships between <i>KIR</i> genotypes and haplotypes with acute lymphoblastic leukemia (ALL) in Saudi patients.</p><p><strong>Methods: </strong>A total of 259 Saudi subjects including 145 cases of acute lymphoblastic leukemia (ALL) and 114 healthy controls living in Riyadh were genotyped for 16 <i>KIR</i> genes and the two <i>HLA-C1</i> and <i>-C2</i> allotypes using PCR-SSP genotyping method.</p><p><strong>Results: </strong>A significant high frequency of the two inhibitory <i>KIR</i> genes; <i>2DL1</i> (OR = 2.4; <i>p</i> < 0.0001) and <i>3DL1</i>(OR = 10.87; <i>p</i> = 0.0068) in ALL compared to healthy group was observed. In contrast, the activating <i>2DS4</i> gene was significantly higher in healthy controls (OR = 0.15, <i>p</i> < 0.0001) compared to ALL patients. Haplotype analysis shows that BX haplogroup was strongly associated with the occurrence of ALL (OR = 4.39; <i>p</i> < 0.0001). Further combinatory analysis of <i>KIR</i> genes with their <i>HLA-C1</i> and <i>-C2</i> ligands demonstrated strong statistically protective effect of the <i>2DS1-C2</i> combination from ALL (OR = 0.06; <i>p</i> = 0.0003).</p><p><strong>Conclusion: </strong>This study presents strong evidence supporting the connection between certain <i>KIR</i> genotypes, haplotypes, and <i>KIR-HLA</i> combinations with acute ALL in the Saudi population. The heightened occurrence of inhibitory <i>KIR</i> genes (<i>2DL1</i> and <i>3DL1</i>) and the BX haplotype in ALL patients indicates a possible involvement of these genetic variability with the dysfunctional of NK cells in the context of ALL disease.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"31 ","pages":"17534259251314774"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004944","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}

{"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}

{"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}

{"title":"Circulating MiR-126 as a potential biomarker in Egyptian colorectal cancer patients: A case-control study.","authors":"Rasha Ahmed Ghorab, Shaimaa H Fouad, Ahmed F Sherief, Rana M Taha, Marwa Hamdy, Mohammad M Darwish, Eman M El-Sehsah, Sara I Taha","doi":"10.1177/17534259241308661","DOIUrl":"10.1177/17534259241308661","url":null,"abstract":"<p><strong>Background: </strong>Globally, colorectal cancer (CRC) is among the most prevalent malignant tumors. It is characterized by unlimited proliferation, invasion, and metastasis. MicroRNA-126 (miR-126) has been shown in many studies to play a significant role in CRC, but data regarding its role in CRC Egyptian patients are limited.</p><p><strong>Objectives: </strong>This case-control study aimed to investigate the miR-126 as a potential marker in CRC Egyptian patients and to correlate its expression levels with CRC tumor, node, metastasis (TNM) stage, distant metastasis, and tumor size.</p><p><strong>Methods: </strong>The study included 50 adult Egyptian participants (30 patients with CRC, 10 patients with colorectal adenoma as a pathological control, and 10 healthy controls). MiR-126 expression levels were detected using Real-Time Quantitative PCR (qPCR) along with the endogenous reference gene hsa-miR-103a in all participants.</p><p><strong>Results: </strong>MiR-126 expression was significantly decreased in CRC patients than both control groups. It was associated with advanced TNM stage (<i>p </i>= 0.001) and distant metastasis (<i>p </i>= 0.002). However, it was not correlated with tumor size (<i>p </i>= 0.980), carcinoembryonic antigen (CEA) (<i>p </i>= 0.397), and cancer antigen 19-9 (CA19-9) (<i>p </i>= 0.236). The best cut-off point of miR-126 to discriminate CRC from both controls was 0.7 and to discriminate metastatic CRC from non-metastatic CRC was 0.3.</p><p><strong>Conclusions: </strong>Our results suggest that miR-126 could be used as an early marker for CRC detection among Egyptian patients and a good prognostic indicator associated with metastasis.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":" ","pages":"17534259241308661"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876976","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":"Selective IgG binding to the LPS glycolipid core found in bovine colostrum, or milk, during Escherichia coli mastitis influences endotoxin function","authors":"Suzanne M. Hurst, David A. L. Flossdorf, Raveen Koralagamage Don, Anton Pernthaner","doi":"10.1177/17534259241269724","DOIUrl":"https://doi.org/10.1177/17534259241269724","url":null,"abstract":"The dynamic interplay between intramammary IgG, formation of antigen-IgG complexes and effector immune cell function is essential for immune homeostasis within the bovine mammary gland. We explore how changes in the recognition and binding of anti-LPS IgG to the glycolipid “functional” core in milk from healthy or clinically diagnosed Escherichia coli (E. coli) mastitis cows’ controls endotoxin function. In colostrum, we found a varied anti-LPS IgG repertoire and novel soluble LPS/IgG complexes with direct IgG binding to the LPS glycolipid core. These soluble complexes, absent in milk from healthy lactating cows, were evident in cows diagnosed with E. coli mastitis and correlated with endotoxin-driven inflammation. E. coli mastitis milk displayed a proportional reduction in anti-LPS glycolipid core IgG compared to colostrum. Milk IgG extracts showed that only colostrum IgG attenuated LPS induced endotoxin activity. Furthermore, LPS-stimulated reactive oxygen species (ROS) in milk granulocytes was only suppressed by colostrum IgG, while IgG extracts of neither colostrum nor E. coli mastitis milk influenced N-formylmethionine-leucyl-phenylalanine (fMLP)-stimulated ROS in LPS primed granulocytes. Our findings support bovine intramammary IgG diversity in health and in response to E. coli infection generate milk anti-LPS IgG repertoires that coordinate appropriate LPS innate-adaptive immune responses essential for animal health.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"8 1","pages":"96-118"},"PeriodicalIF":3.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Respiratory bioenergetics is enhanced in human, but not bovine macrophages after exposure to <i>M. bovis</i> PPD: Exploratory insights into overall similar Cellular Metabolic Profiles.","authors":"Marie-Christine Bartens, Sam Willcocks, Dirk Werling, Amanda J Gibson","doi":"10.1177/17534259241296630","DOIUrl":"10.1177/17534259241296630","url":null,"abstract":"<p><p>The role of macrophage (MØ) cellular metabolism and reprogramming during TB infection is of great interest due to the influence of <i>Mycobacterium</i> spp. on MØ bioenergetics. Recent studies have shown that <i>M. tuberculosis</i> induces a TLR2-dependent shift towards aerobic glycolysis, comparable to the established LPS induced pro-inflammatory M1 MØ polarisation. Distinct differences in the metabolic profile of murine and human MØ indicates species-specific differences in bioenergetics. So far, studies examining the metabolic potential of bovine MØ are lacking, thus the basic bioenergetics of bovine and human MØ were explored in response to a variety of innate immune stimuli. Cellular energy metabolism kinetics were measured concurrently for both species on a Seahorse XFe96 platform to generate bioenergetic profiles for the response to the bona-fide TLR2 and TLR4 ligands, FSL-1 and LPS respectively. Despite previous reports of species-specific differences in TLR signalling and cytokine production between human and bovine MØ, we observed similar respiratory profiles for both species. Basal respiration remained constant between stimulated MØ and controls, whereas addition of TLR ligands induced increased glycolysis, as measured by the surrogate parameter ECAR. In contrast to MØ stimulation with <i>M. tuberculosis</i> PPD, another TLR2 ligand, <i>M. bovis</i> PPD treatment significantly enhanced basal respiration rates and glycolysis only in human MØ. Respiratory profiling further revealed significant elevation of ATP-linked OCR and maximal respiration suggesting a strong OXPHOS activation upon <i>M. bovis</i> PPD stimulation in human MØ. Our results provide an exploratory set of data elucidating the basic respiratory profile of bovine vs. human MØ that will not only lay the foundation for future studies to investigate host-tropism of the <i>M. tuberculosis</i> complex but may explain inflammatory differences observed for other zoonotic diseases.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":" ","pages":"136-149"},"PeriodicalIF":2.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675825","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}