{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:14:27Z","timestamp":1792098867574,"version":"4.4.0"},"reference-count":70,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project P4 of the CRU342","award":["427775125"],"award-info":[{"award-number":["427775125"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Quantitative phase imaging (QPI) is a non-invasive, label-free technique used to detect aberrant cell morphologies caused by disease, thus providing a useful diagnostic approach. Here, we evaluated the potential of QPI to differentiate specific morphological changes in human primary T-cells exposed to various bacterial species and strains. Cells were challenged with sterile bacterial determinants, i.e., membrane vesicles or culture supernatants, derived from different Gram-positive and Gram-negative bacteria. Timelapse QPI by digital holographic microscopy (DHM) was applied to capture changes in T-cell morphology over time. After numerical reconstruction and image segmentation, we calculated single cell area, circularity and mean phase contrast. Upon bacterial challenge, T-cells underwent rapid morphological changes such as cell shrinkage, alterations of mean phase contrast and loss of cell integrity. Time course and intensity of this response varied between both different species and strains. The strongest effect was observed for treatment with S. aureus-derived culture supernatants that led to complete lysis of the cells. Furthermore, cell shrinkage and loss of circular shape was stronger in Gram-negative than in Gram-positive bacteria. Additionally, T-cell response to bacterial virulence factors was concentration-dependent, as decreases in cellular area and circularity were enhanced with increasing concentrations of bacterial determinants. Our findings clearly indicate that T-cell response to bacterial stress depends on the causative pathogen, and specific morphological alterations can be detected using DHM.<\/jats:p>","DOI":"10.3390\/cells12050762","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T03:29:46Z","timestamp":1677554986000},"page":"762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Application of Digital Holographic Microscopy to Analyze Changes in T-Cell Morphology in Response to Bacterial Challenge"],"prefix":"10.3390","volume":"12","author":[{"given":"Kari Lavinia","family":"vom Werth","sequence":"first","affiliation":[{"name":"Institute of Hygiene, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3693-9397","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Kemper","sequence":"additional","affiliation":[{"name":"Biomedical Technology Center of the Medical Faculty, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5013-159X","authenticated-orcid":false,"given":"Stefanie","family":"Kampmeier","sequence":"additional","affiliation":[{"name":"Institute of Hygiene, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0649-5185","authenticated-orcid":false,"given":"Alexander","family":"Mellmann","sequence":"additional","affiliation":[{"name":"Institute of Hygiene, University Hospital M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA\u2014J. Am. Med. Assoc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, Regional, and National Sepsis Incidence and Mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13054-021-03862-5","article-title":"Biomarkers for Sepsis: More than Just Fever and Leukocytosis\u2014A Narrative Review","volume":"26","author":"Barichello","year":"2022","journal-title":"Crit. Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1186\/s13054-020-02993-5","article-title":"Biomarkers of Sepsis: Time for a Reappraisal","volume":"24","author":"Pierrakos","year":"2020","journal-title":"Crit. Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1177\/0885066616682940","article-title":"Cytomorphometric Neutrophil and Monocyte Markers May Strengthen the Diagnosis of Sepsis","volume":"33","author":"Mammen","year":"2018","journal-title":"J. Intensive Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1515\/cclm-2018-0979","article-title":"Improvement in Detecting Sepsis Using Leukocyte Cell Population Data (CPD)","volume":"57","author":"Urrechaga","year":"2019","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4103\/JLP.JLP_102_18","article-title":"Volume, Conductivity, and Scatter Parameters of Leukocytes as Early Markers of Sepsis and Treatment Response","volume":"11","author":"Arora","year":"2019","journal-title":"J. Lab. Physicians"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"284","DOI":"10.21276\/apalm.2395","article-title":"Diagnostic Utility of Cell Population Data (CPD) in Sepsis Using Automated Hematology Analysers","volume":"6","author":"Shalini","year":"2019","journal-title":"Ann. Pathol. Lab. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/CCM.0000000000001266","article-title":"Analyzing Neutrophil Morphology, Mechanics, and Motility in Sepsis","volume":"44","author":"Zonneveld","year":"2016","journal-title":"Crit. Care Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41566-018-0253-x","article-title":"Quantitative Phase Imaging in Biomedicine","volume":"12","author":"Park","year":"2018","journal-title":"Nat. Photonics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4170","DOI":"10.3390\/s130404170","article-title":"Quantitative Phase Imaging Techniques for the Study of Cell Pathophysiology: From Principles to Applications","volume":"13","author":"Lee","year":"2013","journal-title":"Sensors"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"A52","DOI":"10.1364\/AO.47.000A52","article-title":"Digital Holographic Microscopy for Live Cell Applications and Technical Inspection","volume":"47","author":"Kemper","year":"2008","journal-title":"Appl. Opt."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"El-Schich, Z., Janicke, B., Alm, K., Dizeyi, N., Persson, L.J., and Gj\u00f6rloff Wingren, A. (2020). Discrimination between Breast Cancer Cells and White Blood Cells by Non-Invasive Measurements: Implications for a Novel in Vitro-Based Circulating Tumor Cell Model Using Digital Holographic Cytometry. Appl. Sci., 10.","DOI":"10.3390\/app10144854"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/cncy.21727","article-title":"Digital Holographic Microscopy as Screening Tool for Cervical Cancer Preliminary Study","volume":"124","author":"Benzerdjeb","year":"2016","journal-title":"Cancer Cytopathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"031002","DOI":"10.1088\/2515-7647\/ab8a58","article-title":"Overview of Cell Motility-Based Sickle Cell Disease Diagnostic System in Shearing Digital Holographic Microscopy","volume":"2","author":"Anand","year":"2020","journal-title":"JPhys Photonics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1039\/C8LC00350E","article-title":"Label-Free, High-Throughput Detection of P. Falciparum Infection in Sphered Erythrocytes with Digital Holographic Microscopy","volume":"18","author":"Ugele","year":"2018","journal-title":"Lab Chip"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1364\/OE.442321","article-title":"COVID-19 Detection from Red Blood Cells Using Highly Comparative Time-Series Analysis (HCTSA) in Digital Holographic Microscopy","volume":"30","author":"Santaniello","year":"2022","journal-title":"Opt. Express"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"953","DOI":"10.21037\/atm-19-3173","article-title":"Reviewing the Value of Leukocytes Cell Population Data (CPD) in the Management of Sepsis","volume":"8","author":"Urrechaga","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13252","DOI":"10.1038\/srep13252","article-title":"Virulence from Vesicles: Novel Mechanisms of Host Cell Injury by Escherichia Coli O104:H4 Outbreak Strain","volume":"5","author":"Kunsmann","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1160\/TH10-02-0140","article-title":"Differential Cytotoxic Actions of Shiga Toxin 1 and Shiga Toxin 2 on Microvascular and Macrovascular Endothelial Cells","volume":"105","author":"Bauwens","year":"2011","journal-title":"Thromb. Haemost."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sela, U., Euler, C.W., Correa da Rosa, J., and Fischetti, V.A. (2018). Strains of Bacterial Species Induce a Greatly Varied Acute Adaptive Immune Response: The Contribution of the Accessory Genome. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006726"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shepherd, F.R., and McLaren, J.E. (2020). T Cell Immunity to Bacterial Pathogens: Mechanisms of Immune Control and Bacterial Evasion. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176144"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"vom Werth, K.L., W\u00f6rmann, T., Kemper, B., K\u00fcmpers, P., Kampmeier, S., and Mellmann, A. (2022). Investigating Morphological Changes of T-Lymphocytes after Exposure with Bacterial Determinants for Early Detection of Septic Conditions. Microorganisms, 10.","DOI":"10.3390\/microorganisms10020391"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"ofy313","DOI":"10.1093\/ofid\/ofy313","article-title":"Sepsis in Intensive Care Unit Patients: Worldwide Data from the Intensive Care over Nations Audit","volume":"5","author":"Sakr","year":"2018","journal-title":"Open Forum Infect. Dis."},{"key":"ref_25","unstructured":"GBD 2019 Antimicrobial Resistance Collaborators (2022). Global Mortality Associated with 33 Bacterial Pathogens in 2019: A Systematic Analysis for the Global Burden of Disease Study 2019. Lancet, 400, 2248."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"213","DOI":"10.4161\/viru.27024","article-title":"Gram-Positive and Gram-Negative Bacterial Toxins in Sepsis: A Brief Review","volume":"5","author":"Ramachandran","year":"2014","journal-title":"Virulence"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3201\/eid0502.990206","article-title":"Bacterial Toxins: Friends or Foes?","volume":"5","author":"Schmitt","year":"1999","journal-title":"Emerg. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Macion, A., Wyszy\u0144ska, A., and Godlewska, R. (2021). Delivery of Toxins and Effectors by Bacterial Membrane Vesicles. Toxins (Basel)., 13.","DOI":"10.3390\/toxins13120845"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri3837","article-title":"Immune Modulation by Bacterial Outer Membrane Vesicles","volume":"15","author":"Ferrero","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1136\/gutjnl-2018-317726","article-title":"Increased Levels of Systemic LPS-Positive Bacterial Extracellular Vesicles in Patients with Intestinal Barrier Dysfunction","volume":"69","author":"Tulkens","year":"2020","journal-title":"Gut"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.thromres.2020.08.013","article-title":"Bacterial Outer Membrane Vesicles Induce Disseminated Intravascular Coagulation through the Caspase-11-Gasdermin D Pathway","volume":"196","author":"Peng","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17434","DOI":"10.1038\/s41598-017-16363-9","article-title":"Escherichia Coli Outer Membrane Vesicles Can Contribute to Sepsis Induced Cardiac Dysfunction","volume":"7","author":"Svennerholm","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1128\/iai.55.9.2155-2163.1987","article-title":"Ingestion of Staphylococcus Aureus by Bovine Endothelial Cells Results in Time- and Inoculum-Dependent Damage to Endothelial Cell Monolayers","volume":"55","author":"Vann","year":"1987","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/jac\/dkp241","article-title":"Methicillin-Resistant Staphylococcus Aureus Strain USA300: Origin and Epidemiology","volume":"64","author":"Tenover","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1093\/infdis\/jiw444","article-title":"Life after USA300: The Rise and Fall of a Superbug","volume":"215","author":"Planet","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3201\/eid1302.060924","article-title":"Methicillin-Resistant Staphylococcus Aureus ST398 in Humans and Animals, Central Europe","volume":"13","author":"Witte","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1128\/jb.152.3.1241-1247.1982","article-title":"Cloning of the Chromosomal Determinants Encoding Hemolysin Production and Mannose-Resistant Hemagglutination in Escherichia Coli","volume":"152","author":"Berger","year":"1982","journal-title":"J. Bacteriol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1128\/iai.48.2.486-491.1985","article-title":"Serotypes, Hemolysin Production, and Receptor Recognition of Escherichia Coli Strains Associated with Neonatal Sepsis and Meningitis","volume":"48","author":"Korhonen","year":"1985","journal-title":"Infect. Immun."},{"key":"ref_39","unstructured":"Neidhardt FCCurtiss RIngraham JLLin ECCLow KBMagasanik BReznikoff WSRiley MSchaechter MUmbarger, H.E. (1996). Escherichia coli and Salmonella: Cellular and Molecular Biology, ASM Press. [2nd ed.]."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bielaszewska, M., R\u00fcter, C., Kunsmann, L., Greune, L., Bauwens, A., Zhang, W., Kuczius, T., Kim, K.S., Mellmann, A., and Schmidt, M.A. (2013). Enterohemorrhagic Escherichia Coli Hemolysin Employs Outer Membrane Vesicles to Target Mitochondria and Cause Endothelial and Epithelial Apoptosis. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003797"},{"key":"ref_41","first-page":"117860I","article-title":"Enhanced Quantitative Phase Imaging in Mach-Zehnder Interferometer-Based Digital Holographic Microscopy by Modulation of the Object Illumination with an Electrically Focus Tunable Lens","volume":"11786","author":"Kemper","year":"2021","journal-title":"Proc. SPIE"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"034005","DOI":"10.1117\/1.2204609","article-title":"Investigation of Living Pancreas Tumor Cells by Digital Holographic Microscopy","volume":"11","author":"Kemper","year":"2006","journal-title":"J. Biomed. Opt."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1364\/OL.42.000227","article-title":"Simple and Fast Spectral Domain Algorithm for Quantitative Phase Imaging of Living Cells with Digital Holographic Microscopy","volume":"42","author":"Min","year":"2017","journal-title":"Opt. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/cyto.a.23082","article-title":"Quantitative Phase Imaging for Cell Culture Quality Control","volume":"91","author":"Kastl","year":"2017","journal-title":"Cytom. Part A"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An Open-Source Platform for Biological-Image Analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.molimm.2021.02.027","article-title":"Immunomodulatory Roles and Novel Applications of Bacterial Membrane Vesicles","volume":"134","author":"Gilmore","year":"2021","journal-title":"Mol. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"D325","DOI":"10.1093\/nar\/gki008","article-title":"VFDB: A Reference Database for Bacterial Virulence Factors","volume":"33","author":"Chen","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_48","unstructured":"van der Poll, T., and Opal, S.M. (2008). The Lancet Infectious Diseases, Elsevier."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.cmi.2016.06.020","article-title":"Post-Invasion Events after Infection with Staphylococcus Aureus Are Strongly Dependent on Both the Host Cell Type and the Infecting S. Aureus Strain","volume":"22","author":"Strobel","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.micres.2017.08.006","article-title":"Apoptosis Induced by Staphylococcus Aureus Toxins","volume":"205","author":"Zhang","year":"2017","journal-title":"Microbiol. Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Nygaard, T.K., Pallister, K.B., DuMont, A.L., DeWald, M., Watkins, R.L., Pallister, E.Q., Malone, C., Griffith, S., Horswill, A.R., and Torres, V.J. (2012). Alpha-Toxin Induces Programmed Cell Death of Human T Cells, B Cells, and Monocytes during USA 300 Infection. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036532"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e00071-16","DOI":"10.1128\/mSphere.00071-16","article-title":"Phenotypes and Virulence among Staphylococcus Aureus USA100, USA200, USA300, USA400, and USA600 Clonal Lineages","volume":"1","author":"King","year":"2016","journal-title":"mSphere"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/nri.2016.147","article-title":"Programmed Cell Death as a Defence against Infection","volume":"17","author":"Jorgensen","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1152\/nips.01519.2004","article-title":"Morphological Features of Cell Death","volume":"19","author":"Ziegler","year":"2004","journal-title":"Physiology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41420-021-00616-8","article-title":"Deep Learning with Digital Holographic Microscopy Discriminates Apoptosis and Necroptosis","volume":"7","author":"Verduijn","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"E488","DOI":"10.1073\/pnas.1714765115","article-title":"Distinctive Roles of Age, Sex, and Genetics in Shaping Transcriptional Variation of Human Immune Responses to Microbial Challenges","volume":"115","author":"Piasecka","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Macia, L., Nanan, R., Hosseini-Beheshti, E., and Grau, G.E. (2020). Host-and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010107"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Thay, B., Wai, S.N., and Oscarsson, J. (2013). Staphylococcus Aureus \u03b1-Toxin-Dependent Induction of Host Cell Death by Membrane-Derived Vesicles. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054661"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Jin, J.S., Kwon, S.-O., Moon, D.C., Gurung, M., Lee, J.H., Kim, S.I., and Lee, J.C. (2011). Acinetobacter Baumannii Secretes Cytotoxic Outer Membrane Protein A via Outer Membrane Vesicles. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017027"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3389\/fmicb.2020.00057","article-title":"The Uptake, Trafficking, and Biodistribution of Bacteroides Thetaiotaomicron Generated Outer Membrane Vesicles","volume":"11","author":"Jones","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.3389\/fmicb.2019.03026","article-title":"Cracking Open Bacterial Membrane Vesicles","volume":"10","author":"Nagakubo","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.micpath.2016.02.014","article-title":"Variation among Staphylococcus Aureus Membrane Vesicle Proteomes Affects Cytotoxicity of Host Cells","volume":"93","author":"Jeon","year":"2016","journal-title":"Microb. Pathog."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fimmu.2020.00080","article-title":"Streptococcal Extracellular Membrane Vesicles Are Rapidly Internalized by Immune Cells and Alter Their Cytokine Release","volume":"11","author":"Mehanny","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1574-6968.2012.02549.x","article-title":"Klebsiella Pneumoniae Secretes Outer Membrane Vesicles That Induce the Innate Immune Response","volume":"331","author":"Lee","year":"2012","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1016\/j.immuni.2021.10.012","article-title":"The Immunology of Sepsis","volume":"54","author":"Wiersinga","year":"2021","journal-title":"Immunity"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1084\/jem.20021633","article-title":"Regulatory T Cells Selectively Express Toll-like Receptors and Are Activated by Lipopolysaccharide","volume":"197","author":"Caramalho","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/j.1365-2249.2010.04091.x","article-title":"Modulation of Immune Responses through Direct Activation of Toll-like Receptors to T Cells","volume":"160","author":"Liu","year":"2010","journal-title":"Clin. Exp. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1515\/cclm-2021-0192","article-title":"Monocyte Distribution Width (MDW) Parameter as a Sepsis Indicator in Intensive Care Units","volume":"59","author":"Piva","year":"2021","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1097\/CCM.0000000000003342","article-title":"Epidemiology and Costs of Sepsis in the United States-an Analysis Based on Timing of Diagnosis and Severity Level","volume":"46","author":"Paoli","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1164\/rccm.201609-1848OC","article-title":"The Timing of Early Antibiotics and Hospital Mortality in Sepsis","volume":"196","author":"Liu","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/5\/762\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:44:08Z","timestamp":1760121848000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/5\/762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,27]]},"references-count":70,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["cells12050762"],"URL":"https:\/\/doi.org\/10.3390\/cells12050762","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,27]]}}}