{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:18:01Z","timestamp":1791321481835,"version":"4.3.1"},"reference-count":74,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T00:00:00Z","timestamp":1733702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["I85F21001420005"],"award-info":[{"award-number":["I85F21001420005"]}]},{"name":"Italian Ministry of Health","award":["#DSB.AD007228"],"award-info":[{"award-number":["#DSB.AD007228"]}]},{"name":"Italian National Research Council","award":["I85F21001420005"],"award-info":[{"award-number":["I85F21001420005"]}]},{"name":"Italian National Research Council","award":["#DSB.AD007228"],"award-info":[{"award-number":["#DSB.AD007228"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Lipopolysaccharide (LPS) is a potent endotoxin released at high concentrations in acute infections, causing massive host inflammatory response. Accumulating evidence indicates that dysbiosis-associated chronic low levels of circulating LPS can sustain a prolonged sterile low-grade inflammation that increases the risk of several non-communicable diseases. Interventions aimed at increasing the abundance of beneficial\/probiotic bacteria, including Akkermansia muciniphila, result in reduced inflammation, favoring metabolic and immune health. Immunosuppression is a common feature in conditions of chronic inflammation, and dendritic cells (DCs) represent key targets given their ability to shift the balance toward immunity or tolerance. In this study, the effects of low concentrations of LPS from pathogenic (Escherichia coli and Salmonella enterica) and probiotic (Akkermansia muciniphila) bacterial species on human DC generation and functions were compared. We report that monocyte precursor priming with Escherichia coli and Salmonella enterica LPS forces the differentiation of PD-L1-expressing DCs, releasing high levels of IL-6 and IL-10, and impairs their capacity to drive full TCR-V\u03b42 T cell activation. Conversely, comparable concentrations of Akkermansia muciniphila promoted the generation of DCs with preserved activating potential and immunostimulatory properties. These results shed light on potential mechanisms underlying the impact of low endotoxemia on disease risk and pathogenesis, and increase our understanding of the immunomodulatory effects of Akkermansia muciniphila.<\/jats:p>","DOI":"10.3390\/biom14121571","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T04:15:03Z","timestamp":1733804103000},"page":"1571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Akkermansia muciniphila- and Pathogenic Bacteria-Derived Endotoxins Differently Regulate Human Dendritic Cell Generation and \u03b3\u03b4 T Lymphocyte Activation"],"prefix":"10.3390","volume":"14","author":[{"given":"Veronica","family":"Fertitta","sequence":"first","affiliation":[{"name":"Department of Environment and Health, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Varano","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4001-607X","authenticated-orcid":false,"given":"Manuela","family":"Del Corn\u00f2","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6206-8498","authenticated-orcid":false,"given":"Paola","family":"Fortini","sequence":"additional","affiliation":[{"name":"Department of Environment and Health, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3533-4265","authenticated-orcid":false,"given":"Anna","family":"Aureli","sequence":"additional","affiliation":[{"name":"Institute of Translational Pharmacology, National Research Council, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9439-081X","authenticated-orcid":false,"given":"Lucia","family":"Conti","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1111\/lam.13333","article-title":"Gut-organ axis: A microbial outreach and networking","volume":"72","author":"Ahlawat","year":"2021","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev.biochem.71.110601.135414","article-title":"Lipopolysaccharide endotoxins","volume":"71","author":"Raetz","year":"2002","journal-title":"Annu. Rev. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"747","DOI":"10.4014\/jmb.2312.12031","article-title":"Diet-Induced Gut Dysbiosis and Leaky Gut Syndrome","volume":"34","author":"Chae","year":"2024","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3109\/08830185.2015.1087518","article-title":"The Characteristics and Function of Bacterial Lipopolysaccharides and Their Endotoxic Potential in Humans","volume":"35","author":"Gnauck","year":"2016","journal-title":"Int. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Manilla, V., Di Tommaso, N., Santopaolo, F., Gasbarrini, A., and Ponziani, F.R. (2023). Endotoxemia and Gastrointestinal Cancers: Insight into the Mechanisms Underlying a Dangerous Relationship. Microorganisms, 11.","DOI":"10.3390\/microorganisms11020267"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.4049\/jimmunol.137.4.1329","article-title":"The interaction of Escherichia coli with normal human serum: The kinetics of serum-mediated lipopolysaccharide release and its dissociation from bacterial killing","volume":"137","author":"Tesh","year":"1986","journal-title":"J. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1128\/IAI.68.5.2566-2572.2000","article-title":"Outer membrane protein A, peptidoglycan-associated lipoprotein, and murein lipoprotein are released by Escherichia coli bacteria into serum","volume":"68","author":"Hellman","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1146\/annurev.micro.091208.073413","article-title":"Biological functions and biogenesis of secreted bacterial outer membrane vesicles","volume":"64","author":"Kulp","year":"2010","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1128\/IAI.68.5.2410-2417.2000","article-title":"Lipopolysaccharide-binding protein and phospholipid transfer protein release lipopolysaccharides from gram-negative bacterial membranes","volume":"68","author":"Vesy","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e12474","DOI":"10.1002\/jev2.12474","article-title":"Characterisation of LPS+ bacterial extracellular vesicles along the gut-hepatic portal vein-liver axis","volume":"13","author":"Jain","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.biochi.2015.06.020","article-title":"Metabolic endotoxemia with obesity: Is it real and is it relevant?","volume":"124","author":"Boutagy","year":"2016","journal-title":"Biochimie"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.metabol.2016.12.009","article-title":"Metabolic endotoxemia and diabetes mellitus: A systematic review","volume":"68","author":"Gomes","year":"2017","journal-title":"Metabolism"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13024-024-00722-y","article-title":"The endotoxin hypothesis of Alzheimer\u2019s disease","volume":"19","author":"Brown","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1002\/mds.29432","article-title":"The Endotoxin Hypothesis of Parkinson\u2019s Disease","volume":"38","author":"Brown","year":"2023","journal-title":"Mov. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kang, M., Edmundson, P., Araujo-Perez, F., McCoy, A.N., Galanko, J., and Keku, T.O. (2013). Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-91"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"73711","DOI":"10.18632\/oncotarget.12449","article-title":"Lipopolysaccharide increases the release of VEGF-C that enhances cell motility and promotes lymphangiogenesis and lymphatic metastasis through the TLR4- NF-\u03baB\/JNK pathways in colorectal cancer","volume":"7","author":"Zhu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e1805007","DOI":"10.1002\/adma.201805007","article-title":"Trapping of Lipopolysaccharide to Promote Immunotherapy against Colorectal Cancer and Attenuate Liver Metastasis","volume":"30","author":"Song","year":"2018","journal-title":"Adv. Mater."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1007\/s11605-023-05654-4","article-title":"Gut Barrier Dysfunction and Bacterial Lipopolysaccharides in Colorectal Cancer","volume":"27","author":"Li","year":"2023","journal-title":"J. Gastrointest. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1177\/0884533611434934","article-title":"Of microbes and meals: The health consequences of dietary endotoxemia","volume":"27","author":"Kelly","year":"2012","journal-title":"Nutr. Clin. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Erlanson-Albertsson, C., and Stenkula, K.G. (2021). The Importance of Food for Endotoxemia and an Inflammatory Response. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179562"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1002\/1873-3468.14328","article-title":"Lipopolysaccharide and the gut microbiota: Considering structural variation","volume":"596","author":"Mohr","year":"2022","journal-title":"FEBS Lett."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lin, T.-L., Shu, C.-C., Chen, Y.-M., Lu, J.-J., Wu, T.-S., Lai, W.-F., Tzeng, C.-M., Lai, H.-C., and Lu, C.-C. (2020). Like Cures Like: Pharmacological Activity of Anti-Inflammatory Lipopolysaccharides From Gut Microbiome. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00554"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"de Gouveia, M.I.M., Bernalier-Donadille, A., and Jubelin, G. (2024). in the Human Gut: Dynamics and Ecological Roles in Health and Disease. Biology, 13.","DOI":"10.3390\/biology13030142"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kittana, H., Gomes-Neto, J.C., Heck, K., Geis, A.L., Mu\u00f1oz, R.R.S., Cody, L.A., Schmaltz, R.J., Bindels, L.B., Sinha, R., and Hostetter, J.M. (2018). Commensal. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02318"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rodrigues, V.F., Elias-Oliveira, J., Pereira, S., Pereira, J.A., Barbosa, S.C., Machado, M.S.G., and Carlos, D. (2022). Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.934695"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mruk-Mazurkiewicz, H., Kulaszy\u0144ska, M., Czarnecka, W., Podk\u00f3wka, A., Ekstedt, N., Zawodny, P., Wierzbicka-Wo\u015b, A., Marlicz, W., Skupin, B., and Stachowska, E. (2024). Insights into the Mechanisms of Action of. Nutrients, 16.","DOI":"10.3390\/nu16111695"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/femsle\/fnac103","article-title":"Akkermansia muciniphila attenuates LPS-induced acute kidney injury by inhibiting TLR4\/NF-\u03baB pathway","volume":"369","author":"Shi","year":"2022","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Shi, M., Yue, Y., Ma, C., Dong, L., and Chen, F. (2022). Pasteurized. Nutrients, 14.","DOI":"10.3390\/nu14040764"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Faghfuri, E., and Gholizadeh, P. (2024). The role of Akkermansia muciniphila in colorectal cancer: A double-edged sword of treatment or disease progression?. Biomed. Pharmacother., 173.","DOI":"10.1016\/j.biopha.2024.116416"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cell.2014.03.011","article-title":"Role of the microbiota in immunity and inflammation","volume":"157","author":"Belkaid","year":"2014","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nri2515","article-title":"The gut microbiota shapes intestinal immune responses during health and disease","volume":"9","author":"Round","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.imlet.2023.01.003","article-title":"The intestinal microenvironment shapes macrophage and dendritic cell identity and function","volume":"253","author":"Filardy","year":"2023","journal-title":"Immunol. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s00018-016-2317-8","article-title":"Molecular mechanisms involved in dendritic cell dysfunction in cancer","volume":"74","author":"Tang","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4835","DOI":"10.1038\/s41467-020-18570-x","article-title":"PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade","volume":"11","author":"Peng","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.iotech.2019.06.002","article-title":"The emerging role of \u03b3\u03b4 T cells in cancer immunotherapy","volume":"1","author":"Nussbaumer","year":"2019","journal-title":"Immunooncol. Technol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"252","DOI":"10.4049\/jimmunol.174.1.252","article-title":"Reciprocal activating interaction between dendritic cells and pamidronate-stimulated gammadelta T cells: Role of CD86 and inflammatory cytokines","volume":"174","author":"Conti","year":"2005","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1007\/s00262-020-02805-3","article-title":"The subtle interplay between gamma delta T lymphocytes and dendritic cells: Is there a role for a therapeutic cancer vaccine in the era of combinatorial strategies?","volume":"70","author":"Galati","year":"2021","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yang, Y., Xu, C., Wu, D., Wang, Z., Wu, P., Li, L., Huang, J., and Qiu, F. (2018). \u03b3\u03b4 T Cells: Crosstalk Between Microbiota, Chronic Inflammation, and Colorectal Cancer. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01483"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Costanzo, A.E., Taylor, K.R., Dutt, S., Han, P.P., Fujioka, K., and Jameson, J.M. (2015). Obesity impairs \u03b3\u03b4 T cell homeostasis and antiviral function in humans. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120918"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Donninelli, G., Del Corn\u00f2, M., Pierdominici, M., Scazzocchio, B., Var\u00ec, R., Varano, B., Pacella, I., Piconese, S., Barnaba, V., and D\u2019archivio, M. (2017). Distinct Blood and Visceral Adipose Tissue Regulatory T Cell and Innate Lymphocyte Profiles Characterize Obesity and Colorectal Cancer. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00643"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Abhilasha, K.V., and Marathe, G.K. (2021). Bacterial lipoproteins in sepsis. Immunobiology, 226.","DOI":"10.1016\/j.imbio.2021.152128"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1084\/jem.20030335","article-title":"Lipopolysaccharide or whole bacteria block the conversion of inflammatory monocytes into dendritic cells in vivo","volume":"198","author":"Rotta","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1002\/jlb.65.2.232","article-title":"Lipopolysaccharide can block the potential of monocytes to differentiate into dendritic cells","volume":"65","author":"Palucka","year":"1999","journal-title":"J. Leukoc. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4102","DOI":"10.1182\/blood-2006-03-008946","article-title":"Involvement of suppressors of cytokine signaling in toll-like receptor-mediated block of dendritic cell differentiation","volume":"108","author":"Bartz","year":"2006","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1189\/jlb.0909615","article-title":"Salmonella inhibits monocyte differentiation into CD11c hi MHC-II hi cells in a MyD88-dependent fashion","volume":"87","author":"Wick","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4792","DOI":"10.4049\/jimmunol.171.9.4792","article-title":"Novel and detrimental effects of lipopolysaccharide on in vitro generation of immature dendritic cells: Involvement of mitogen-activated protein kinase p38","volume":"171","author":"Xie","year":"2003","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s11481-024-10115-z","article-title":"JAK1\/2 Regulates Synergy Between Interferon Gamma and Lipopolysaccharides in Microglia","volume":"19","author":"Young","year":"2024","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4798","DOI":"10.1128\/JVI.03681-14","article-title":"HIV-1-induced impairment of dendritic cell cross talk with \u03b3\u03b4 T lymphocytes","volume":"89","author":"Cardone","year":"2015","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Baggio, C., Ramaschi, G.E., Oliviero, F., Ramonda, R., Sfriso, P., Trevisi, L., Cignarella, A., and Bolego, C. (2023). Sex-dependent PD-L1\/sPD-L1 trafficking in human endothelial cells in response to inflammatory cytokines and VEGF. Biomed. Pharmacother., 162.","DOI":"10.1016\/j.biopha.2023.114670"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/eji.201040979","article-title":"PD-L1 expression on tolerogenic APCs is controlled by STAT-3","volume":"41","author":"Strebovsky","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3390\/immuno2030030","article-title":"Lipopolysaccharide-Induced Immunological Tolerance in Monocyte-Derived Dendritic Cells","volume":"2","author":"Mbongue","year":"2022","journal-title":"Immuno"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.humic.2018.01.001","article-title":"Gut microbiota diversity according to dietary habits and geographical provenance","volume":"7-8","author":"Senghor","year":"2018","journal-title":"Hum. Microbiome J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"135478","DOI":"10.1016\/j.foodchem.2023.135478","article-title":"Effects of microbial-derived biotics (meta\/pharma\/post-biotics) on the modulation of gut microbiome and metabolome; general aspects and emerging trends","volume":"411","author":"Sadeghi","year":"2023","journal-title":"Food Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s12602-023-10058-6","article-title":"The Effect of Akkermansia muciniphila and Its Outer Membrane Vesicles on MicroRNAs Expression of Inflammatory and Anti-inflammatory Pathways in Human Dendritic Cells","volume":"16","author":"Mofrad","year":"2024","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Pe\u00f1a-Cearra, A., Palacios, A., Pellon, A., Castelo, J., Pasco, S.T., Seoane, I., Barriales, D., Martin, J.E., Pascual-Itoiz, M.A., and Gonzalez-Lopez, M. (2024). Akkermansia muciniphila-induced trained immune phenotype increases bacterial intracellular survival and attenuates inflammation. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-05867-6"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ganesh, B.P., Klopfleisch, R., Loh, G., and Blaut, M. (2013). Commensal Akkermansia muciniphila exacerbates gut inflammation in Salmonella Typhimurium-infected gnotobiotic mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074963"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Luo, Y., Lan, C., Li, H., Ouyang, Q., Kong, F., Wu, A., Ren, Z., Tian, G., Cai, J., and Yu, B. (2022). Rational consideration of Akkermansia muciniphila targeting intestinal health: Advantages and challenges. NPJ Biofilms Microbiomes, 8.","DOI":"10.1038\/s41522-022-00338-4"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Lerouge, S. (2012). Introduction to sterilization: Definitions and challenge. Steriliz. Biomater. Med. Devices, 1\u201319.","DOI":"10.1533\/9780857096265.1"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.cell.2016.04.007","article-title":"Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans","volume":"165","author":"Vatanen","year":"2016","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.imlet.2021.03.008","article-title":"Protective effect of Bacteroides fragilis LPS on Escherichia coli LPS-induced inflammatory changes in human monocytic cells and in a rheumatoid arthritis mouse model","volume":"233","author":"Kitamura","year":"2021","journal-title":"Immunol. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1007\/s10753-013-9737-5","article-title":"Endotoxin tolerance induced by lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli: Alternations in Toll-like receptor 2 and 4 signaling pathway","volume":"37","author":"Sun","year":"2014","journal-title":"Inflammation"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"8411","DOI":"10.1038\/s41467-024-52683-x","article-title":"The lipooligosaccharide of the gut symbiont Akkermansia muciniphila exhibits a remarkable structure and TLR signaling capacity","volume":"15","author":"Tytgat","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1134\/S0362119715010028","article-title":"Endotoxin theory of atherosclerosis","volume":"41","author":"Anikhovskaya","year":"2015","journal-title":"Hum. Phisiology"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Kruglikov, I.L., and Scherer, P.E. (2021). Preexisting and inducible endotoxemia as crucial contributors to the severity of COVID-19 outcomes. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009306"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Xiao, Z., Wang, R., Wang, X., Yang, H., Dong, J., He, X., Yang, Y., Guo, J., Cui, J., and Zhou, Z. (2023). Impaired function of dendritic cells within the tumor microenvironment. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1213629"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Liu, J., Chen, Z., Li, Y., Zhao, W., Wu, J., and Zhang, Z. (2021). PD-1\/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.731798"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.immuni.2007.05.016","article-title":"Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses","volume":"27","author":"Butte","year":"2007","journal-title":"Immunity"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.immuni.2024.01.013","article-title":"The B7:CD28 family and friends: Unraveling coinhibitory interactions","volume":"57","author":"Burke","year":"2024","journal-title":"Immunity"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1158\/2326-6066.CIR-17-0316","article-title":"PD-L1 Binds to B7-1 Only","volume":"6","author":"Chaudhri","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.atherosclerosis.2008.06.018","article-title":"Ethnic and sex differences in circulating endotoxin levels: A novel marker of atherosclerotic and cardiovascular risk in a British multi-ethnic population","volume":"203","author":"Miller","year":"2009","journal-title":"Atherosclerosis"},{"key":"ref_71","first-page":"211","article-title":"Determinants of the extent and duration of STAT3 signaling","volume":"1","author":"Groner","year":"2012","journal-title":"JAKSTAT"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Cui, T.X., Brady, A.E., Zhang, Y.J., Anderson, C., and Popova, A.P. (2023). IL-17a-producing \u03b3\u03b4T cells and NKG2D signaling mediate bacterial endotoxin-induced neonatal lung injury: Implications for bronchopulmonary dysplasia. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1156842"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.imbio.2014.02.012","article-title":"STAT3-silenced human dendritic cells have an enhanced ability to prime IFN\u03b3 production by both \u03b1\u03b2 and \u03b3\u03b4 T lymphocytes","volume":"219","author":"Sanseverino","year":"2014","journal-title":"Immunobiology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1550618","DOI":"10.1080\/2162402X.2018.1550618","article-title":"PD-1 signaling modulates interferon-\u03b3 production by Gamma Delta (\u03b3\u03b4) T-Cells in response to leukemia","volume":"8","author":"Hoeres","year":"2019","journal-title":"Oncoimmunology"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/12\/1571\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:50:53Z","timestamp":1760115053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/12\/1571"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,9]]},"references-count":74,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["biom14121571"],"URL":"https:\/\/doi.org\/10.3390\/biom14121571","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,9]]}}}