Medical Microbiology and Immunology最新文献

{"title":"Immunomodulatory effect of stress hormones on porcine neutrophil functions during Actinobacillus pleuropneumoniae infection.","authors":"Marta C Bonilla, Simon Lassnig, Michael Wendt, Isabel Hennig-Pauka, Matthias Mörgelin, Maren von Köckritz-Blickwede, Nicole de Buhr","doi":"10.1007/s00430-026-00881-3","DOIUrl":"10.1007/s00430-026-00881-3","url":null,"abstract":"<p><p>Stress contributes to disease outcomes and can influence the signaling and interactions of immune cells. This study aimed to evaluate the influence of three selected stress hormones cortisol, epinephrine and norepinephrine, at in vivo-relevant concentrations, on the antimicrobial activity of porcine neutrophils during infection with Actinobacillus pleuropneumoniae (A.pp). We analyzed whether stress hormones affect the antimicrobial activity of neutrophils. Reactive oxygen species (ROS) production, cell size, and granularity were measured using flow cytometry. Neutrophil extracellular trap (NET) formation was quantified using confocal immunofluorescence microscopy, and transmission electron microscopy was employed to analyze the formation of vesicular NETs. ROS production and NET formation experiments were also conducted under infection with A.pp. The survival of A.pp in the presence of stress hormone-treated neutrophils was assessed. The antimicrobial activity of neutrophils was altered in a concentration-dependent manner by all tested stress hormones: neutrophils produced higher amounts of ROS and released significantly more NETs under A.pp infection, in particular vesicular NET formation. However, A.pp growth in the presence or absence of neutrophils was not affected by stress hormones. Future studies are needed to characterize the role of vesicular NETs as stress response reactions. In conclusion, this study contributes to a better understanding of the innate immune cells, particularly porcine neutrophils, in infections within stressed hosts.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human ex vivo comparison of Escherichia coli and Pseudomonas aeruginosa lipopolysaccharide-induced immune responses and cefiderocol effects in whole blood.","authors":"Lena Pracher, Anselm Jorda, Sabine Eberl, Maria Weber, Markus Zeitlinger","doi":"10.1007/s00430-026-00883-1","DOIUrl":"10.1007/s00430-026-00883-1","url":null,"abstract":"<p><p>Immune dysregulation is central in bacterial sepsis with lipopolysaccharide (LPS) of gram-negative bacteria acting as a key component in innate immune activation. Modulation of the host response by potential immunomodulatory agents may confer benefits. This ex vivo study compared cytokine responses induced by E. coli and P. aeruginosa LPS and evaluated the impact of cefiderocol on LPS-induced immune activation in human whole blood. Whole blood from ten healthy volunteers was stimulated ex vivo with E. coli or P. aeruginosa LPS in the presence or absence of cefiderocol and incubated for 4 h at 37 °C. Plasma concentrations of TNF-α, IL-1β, IL-6, IL-10, IFN-α, IFN-γ, and IL-8 were quantified at 0 h, 2 h, and 4 h using a multiplex immunoassay. Cytokine release was significantly higher after E. coli LPS stimulation than with P. aeruginosa LPS across all analytes. Mean TNF-α area under the curve (AUC₀-₄) was 2379 pg*h/mL with cefiderocol vs 1936 pg*h/mL without (percent difference 18.2% [95% CI, 5.9-31.4]) after E. coli LPS stimulation, and 278 pg/mL vs 242 pg*h/mL (12.9% [4.3-21.5]) after P. aeruginosa LPS stimulation. For IL-6, cefiderocol slightly increased AUC₀-₄ following E. coli LPS stimulation (4584 vs 3635 pg*h/mL; 20.7% [8.3-33.0]) but not with P. aeruginosa LPS (184 vs 201 pg*h/mL; - 9.3% [- 53.7-35.2]). IL-1β, IL-10, IFN-α, IFN-γ, and IL-8 levels were mostly unaffected by cefiderocol. Cefiderocol did not suppress cytokine release in human whole blood. In this study, E. coli LPS elicited a stronger immune response than P. aeruginosa LPS.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Candida albicans hyphae modulate Staphylococcus aureus cell-free supernatant during dual biofilm growth to drive molecular signatures of oral dysplasia.","authors":"Freddy H Marin-Dett, Mateus P Grejo, Valéria Valente, Mariana P Palaçon, Andreia Bufalino, Brian M Peters, Paula A Barbugli","doi":"10.1007/s00430-026-00880-4","DOIUrl":"10.1007/s00430-026-00880-4","url":null,"abstract":"<p><p>Microbes frequently exist as biofilm-embedded multi-species communities where their interactions may establish or exacerbate chronic infection. Recently, fungi and bacteria have been associated with various human tumor microenvironments, suggesting that dynamic cross-kingdom interactions may directly or indirectly contribute to tumor-associated processes. Here, we aimed to investigate whether cell-free supernatants from mono- and dual-species biofilms of the commonly associated fungus Candida albicans and bacterium Staphylococcus aureus could alter human monocyte responses that promote a tumor-related genetic signature in dysplastic oral epithelial (DOK) cells. Treatment of THP-1 monocytes with S. aureus cell-free supernatant increased the production of proinflammatory cytokines (IL-8, IL-1β, and TNF) and CD86 expression. However, exposure to cell-free supernatants from dual-species biofilm suppressed these responses. To determine the fungal virulence factors responsible, C. albicans mutants deleted for genes involved in adhesion (als3Δ/Δ), hyphal growth (efg1Δ/Δ cph1Δ/Δ), or candidalysin production (ece1Δ/Δ) were assessed during co-culture. While candidalysin was dispensable, loss of hyphal growth or the adhesin Als3p phenocopied effects of S. aureus mono-culture treatment. Conditioned medium from THP-1 cells initially challenged with mono- or dual-biofilm cell-free supernatants was applied to DOK cells to assess TP53 and BCL2 gene expression. Conditioned medium from S. aureus treated THP-1 cells led to decreased epithelial TP53, but increased BCL2 expression, which was reversed by the presence of wild-type C. albicans. These phenotypes were similarly dependent on C. albicans hyphal growth during dual-biofilm co-culture. Collectively, our results reveal that fungal-bacterial interactions may shape the monocyte-epithelial axis by orchestrating immune responses that enhance tumor-associated gene expression in dysplastic oral epithelial cells.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting phospholipase A2 with arachidonyl trifluoromethyl ketone modulates macrophage activation during Japanese encephalitis virus infection.","authors":"Alok Kumar, Gajendra Singh, Francesco Zonta, Qiujie Zhu, Anjali Singh, Abhishek Saxena, Devlina Ghosh","doi":"10.1007/s00430-026-00879-x","DOIUrl":"10.1007/s00430-026-00879-x","url":null,"abstract":"<p><p>Phospholipase A₂ (PLA₂) is a crucial enzyme in lipid metabolism and inflammatory signaling, playing a significant role in macrophage activation and neuroinflammation. However, its role in Japanese encephalitis virus (JEV)-mediated immune responses remains unclear. In this study, we show that PLA₂ and its associated receptors, lysophosphatidic acid receptors (LPAR1 and LPAR3), are significantly upregulated at 24 h post-JEV infection, suggesting their involvement in JEV-induced inflammatory responses. To investigate the effect of PLA₂ inhibition, we used arachidonyl trifluoromethyl ketone (AACOCF₃). Molecular docking using AutoDock Vina 1.1.2, supported by Protein Data Bank and AlphaFold structures, indicated that AACOCF₃ interacts with key inflammatory targets including gp91^phox (- 7.9 kcal/mol) and LPAR3 (- 7.8 kcal/mol), suggesting its potential to modulate inflammatory and oxidative pathways. In vitro studies in JEV-infected macrophages demonstrated that AACOCF₃ reduced activation of calcium-dependent cytosolic (c) PLA₂ expression and phosphorylation, LPAR1, 3, MAPK signaling (JNK, ERK1/2, p38), and NF-κB protein levels, along with a reduction in JE viral RNA levels, likely reflecting indirect effects mediated through host pathway modulation. AACOCF₃ also decreased proinflammatory cytokines (IL-1β, TNF-α) and autophagy-related markers (pAkt, LC3-II/I, SQSTM1/p6₂), and reduced expression of the ROS-generating enzyme gp91^phox (NOX2), indicating partial attenuation of inflammatory and oxidative stress-associated pathways. Oxidative stress was assessed via gp91^phox expression, and NF-κB was evaluated at protein level. These findings suggest that PLA₂ contributes to JEV-induced inflammatory signaling, and that its inhibition modulates host responses during infection in vitro, rather than exerting a definitive therapeutic effect.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148032576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epitope mapping and conservation of antigens from the Multi-Cruzi immunoassay platform.","authors":"Eric Dumonteil, Claudia Herrera","doi":"10.1007/s00430-026-00877-z","DOIUrl":"10.1007/s00430-026-00877-z","url":null,"abstract":"<p><p>Infection with the protozoan parasite Trypanosoma cruzi can lead to Chagas disease, and diagnosis of infection mostly relies on serological testing, although no gold standard exists. The evaluation of treatment efficacy is also challenging as seronegativization takes decades to be detected. The Multi-Cruzi platform, which provides a serological profile against 15 parasite antigens, has been proposed as promising alternative for confirmatory diagnostic and monitoring of treatment response. To further evaluate this platform, we performed epitope mapping of the Multi-Cruzi antigens with peptide microarrays, using confirmed T. cruzi positive samples, as well as serologically discordant samples with positive T. cruzi PCR. Epitope conservation among parasite strains was also assessed. We identified multiple linear epitopes among Multi-Cruzi antigens with samples from patients with confirmed serology, although some redundancy in epitopes may limit the breadth of the antibody profile evaluated. On the other hand, this antigen panel showed very limited reactivity with serodiscordant samples with confirmed T. cruzi infection, with weaker recognition of fewer epitopes. Epitope conservation ranged from highly conserved to more variable. The usefulness of this platform may be limited to a fraction of patients and parasite strains. The addition of alternative antigens may help improve the monitoring of treatment response of serodiscordant patients.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unique molecular profiling of monocyte responses to a high dose of DENV-NS1 reflected the effect of NS1 on hemostasis.","authors":"Khwankhao Saisingha, Chernkhwan Kaofai, Naphak Modhiran, Daniel Watterson, Supachai Paiboonpol, Anusorn Pawaputanun, Pornsawan Leaungwutiwong, Borimas Hanboonkunupakarn, Chayasin Mansanguan, Jitra Limthongkul, Marisa Ponpuak, Tuksin Jearanaiwitayakul, Sukathida Ubol","doi":"10.1007/s00430-026-00876-0","DOIUrl":"10.1007/s00430-026-00876-0","url":null,"abstract":"<p><p>The pathogenesis of dengue is complex and requires further study. Infection with the dengue virus can lead to severe dengue, in which patients experience severe plasma leakage and excessive bleeding. The dengue virus non-structural protein 1 (DENV NS1) is among several factors that affect the outcome. The secreted form of this protein induces severe cases through direct and indirect immunopathogenesis mechanisms. Previously, we discovered that the stimulation of blood monocytes by NS1 upregulates transcripts involved in inflammation, and suppresses transcripts involved in antiviral processes. In this study, we examined the specific responses unique to high-dose NS1 exposure of cultured human monocytes. We found that genes involved in hemostasis were altered following NS1 exposure and were associated with platelet activation, fibrinolysis, and hemostatic regulation. Some of these expression changes were also observed in patients with dengue fever (DF) or dengue hemorrhagic fever (DHF). The altered expression of these genes suggests that fibrinolysis is more likely balanced during DF, whereas coagulation may be impaired in DHF.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous quantification of anti-Spike IgG subclasses against various SARS-CoV-2 variants using a multiplex serological assay.","authors":"Marie L Bischof, Pascal Irrgang, Matthias Tenbusch, Oliver T Keppler, Paul R Wratil","doi":"10.1007/s00430-026-00878-y","DOIUrl":"10.1007/s00430-026-00878-y","url":null,"abstract":"<p><p>Recent research indicates that the composition of serum anti-SARS-CoV-2 Spike IgG subclass antibodies changes upon repeated exposure to viral Spike. These antibody subclass dynamics were suggested to impact adaptive immune responses and protection against infection. To characterize the role of the IgG subclass composition in the immune response to SARS-CoV-2, assays that measure virus variant-specific anti-Spike IgG subclass concentrations are needed. Here, we describe an easy-to-use serological method for quantifying anti-Spike IgG subclass antibodies against various SARS-CoV-2 variants in multiplex from less than 10 µL of serum. Our assay enables antigen-independent quantification, making it easily adaptable to emerging variants or other pathogens. We validated our method with 20 sera collected from 10 infection-naïve individuals after the second and third COVID-19 mRNA vaccination. We observed increasing anti-Spike IgG2 and, especially, IgG4 concentrations after the third immunization. More recent Spike variants preserved this pattern with decreased levels of total anti-Spike IgG. Our results showed a strong positive correlation with those from an established flow cytometry-based approach. Our method might help deepen our understanding of immune responses to SARS-CoV-2 and, moreover, help gauge the individual's protection from severe disease.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrauterine exposure to HBsAg attenuates the immune response to hepatitis B vaccine via the miR-155-5p/MyD88 axis of DCs in mouse pups.","authors":"Xufeng Cui, Jia Lian, Yangle Sun, Xiaosheng Zhang, Bihong Ke, Xinyuan Mo, Ying Zhang, Tian Yao, Yandi Li, Linying Gao, Keke Wang, Suping Wang, Yongliang Feng","doi":"10.1007/s00430-026-00875-1","DOIUrl":"10.1007/s00430-026-00875-1","url":null,"abstract":"<p><p>The mechanism of non-/hypo-response to hepatitis B vaccine among infants born to Hepatitis B surface Antigen (HBsAg) positive mothers has not been fully clarified. Intrauterine exposure to HBsAg may alter the innate and adaptive immunity of the offspring, further complicating vaccine response. One potential factor is myeloid differentiation factor 88 (MyD88), which is a key adaptor protein linking innate and adaptive immunity and may be regulated by microRNAs (miRNAs). The study aimed to determine the impacts of intrauterine exposure to HBsAg on the immune response to hepatitis B vaccine in the offspring and the potential mechanisms. In the cohort of infants born to HBsAg positive mothers, three pairs of hepatitis B vaccine non-responsive/responsive infants were matched. And miRNA sequencing and bioinformatics were performed to identify miRNAs that are involved in regulating MyD88. Moreover, to mimic human intrauterine exposure to HBsAg, female Hepatitis B Virus-Transgenic (HBV-Tg) mice were mated with male C57BL/6J mice. After birth, pups including HBV-Tg+ and HBV-Tg− pups were administered 1 µg hepatitis B vaccine according to the 0-2-4week vaccination schedule. Among infants born to HBsAg positive mothers, microRNA-155-5p (miR-155-5p) expression was higher in non-responders than responders. miRNA sequencing and bioinformatics suggested miR-155-5p may regulate MyD88 expression in these neonates. In the animal experiment, pups with intrauterine exposure to HBsAg produced less anti-HBs after vaccination. Flow cytometry showed that both HBV-Tg− pups and HBV-Tg+ pups had less generation of CD4+ T cells, B cells, dendritic cells (DCs), and Germinal Center B (GC B) cells in comparison with wild type (WT) mice pups. Cytokine analysis demonstrated that Interleukin-6 (IL-6) and Interleukin-12 (IL-12) were expressed at lower levels in the pups with intrauterine exposure to HBsAg. Further investigation of MyD88 signaling pathway and miR-155-5p pointed that in DCs of pups with intrauterine exposure to HBsAg, there were lower expression of MyD88 and Nuclear Factor-kappa B (NF-κB), while miR-155-5p was elevated. There is a potential link between intrauterine HBsAg exposure, compromised DC generation and activation, and subsequent suboptimal vaccine response. The current data implied that intrauterine HBsAg exposure may have an inhibitory effect on the MyD88 signaling pathway in DCs, with miR-155-5p potentially negatively regulating MyD88.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute COVID-19 is associated with altered CD8 T-cells indicative of impaired ability to control Epstein-Barr virus reactivation.","authors":"Ulrik Stervbo, Moritz Anft, Krystallenia Paniskaki, Arturo Blazquez-Navarro, Adrian Doevelaar, Sarah Skrzypczyk, Eva Kohut, Julia Kurek, Patrizia Wehler, Sviatlana Kaliszczyk, Kamil Rosiewicz, Felix S Seibert, Bodo Hölzer, Constantin J Thieme, Toralf Roch, Margarethe Justine Konik, Marc Moritz Berger, Thorsten Brenner, Uwe Kölsch, Michael Adamzik, Michael Schmueck-Henneresse, Carmen Scheibenbogen, Sebastian Dolff, Ulf Dittmer, Oliver Witzke, Timm H Westhoff, Nina Babel","doi":"10.1007/s00430-026-00873-3","DOIUrl":"10.1007/s00430-026-00873-3","url":null,"abstract":"<p><p>Increasing evidence suggests that reactivation of latent EBV in patients with COVID-19 may be linked to the development of post-acute sequelae of COVID-19, colloquially known as Long COVID. However, the reason for this co-occurrence of primary infection and reactivation of latent viruses remains elusive. During the first wave of COVID-19, we assessed all major immune cell populations by flow cytometry in a cohort of 61 patients with moderate to critical COVID-19 at the time of hospitalization. Additional blood samples from these patients were biobanked for later analysis. Using these biobanked samples, we evaluated the co-occurrence of CMV, EBV, as well as HHV-6A and -6B by qPCR. EBV was found to be reactivated not only in patients with critical or severe COVID-19 (24/33 patients; 72.72%), but also in patients with moderate COVID-19 disease (19/28; 67.86%) at the time of hospital admission. In contrast, HHV-6A was not detected among any patients, whereas CMV and HHV-6B only occurred in low frewuencies (7.1–12.1% and 10.7–15.2%, respectively). In COVID-19 patients with EBV reactivation, the degree of expression of the T-cell co-stimulatory CD28 and co-expression of CD28 and the integrin CD11a was diminished on CD8 T-cells. In contrast, the frequency of CD8 T-cells expressing the proliferative exhaustion marker CD57 increased. Collectively, these data point to an altered activation phenotype of circulating CD8 T cells and that higher replicative senescence is associated with EBV reactivation. The data presented here suggests an alteration in the CD8 T-cell compartment with impaired ability to control the EBV reactivation in COVID patients.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response of dendritic cells and T cells to virus-like particles formed from norovirus viral protein-1 (VP1N) or chimeric molecules containing a fragment of VP1N and polypeptides of echovirus 30.","authors":"Vladimir Talayev, Dmitry Novikov, Elena Kurkova, Irina Zaichenko, Maria Svetlova, Olga Babaykina, Anna-Maria Zharova, Vladislav Lapin, Dmitry Melentev, Nadezhda Novikova, Alexander Kashnikov, Viktor Novikov","doi":"10.1007/s00430-026-00874-2","DOIUrl":"10.1007/s00430-026-00874-2","url":null,"abstract":"<p><p>Virus-like particles (VLPs) are considered as promising components of vaccines. We studied the response of human dendritic cells (DCs) and naïve CD4+ T cells in vitro and the response of murine T cells in vivo to VLPs derived from VP1N, from a fragment of this protein containing the shell domain and hinge region (SN), or from chimeric molecules obtained by genetic fusion of SN with the VP1, VP2, or VP3 polypeptides of echovirus 30 (SN-VP1E30, SN-VP2E30, and SN-VP3E30). Norovirus VLPs were efficiently endocytosed and stimulated the maturation of monocyte-derived DCs and conventional blood-borne CD1c+CD141− DCs. Chimeric SN-VP2E30 VLPs strongly stimulated DC maturation, SN-VP3E30 VLPs had a weak effect, but a mixture of these VLPs potently induced DC maturation. VLP-treated DCs enhanced cytokine production and increased the ability to induce differentiation of human naïve CD4+ T cells into T helper type 1 cells. Immunization of mice with VP1N VLPs, SN-VP2E30 VLPs or a mixture of SN-VP1E30, SN-VP2E30 and SN-VP3E30 VLPs increases the number of CD4+ splenocytes capable of proliferating in response to the antigens of all particles administered to the mouse, as well as CD8+ splenocytes capable of proliferating in response to VP2E30 or SN-VP1E30. Immunization of mice with VLPs resulted in increased IFN-γ production by splenocytes stimulated ex vivo with VP1N, VP2E30, and SN-VP3E30. In addition, immunization with SN-VP2E30 VLPs resulted in increased IL-5 production by splenocytes in response to specific antigens. The results indicate the ability of norovirus VLPs and chimeric VLPs to induce T cell responses.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}