Henrique Fernando Lopes-Araujo, Wlisses Henrique Veloso Carvalho-Silva, José Leandro Andrade-Santos, Maria Carolina Santos Guedes, Fabrício Oliveira Souto, Luiz Cláudio Arraes De Alencar, Isadora Bandeira De Luna Paes Barreto Brennand, Thayana Karinne Oliveira Monteiro, Kleyverson Feliciano-Santos, José Artur Bogo Chies, Rafael Lima Guimarães
{"title":"CCR5Δ32 polymorphism is associated with increased central memory CD4+ T cells in virologically suppressed people living with HIV on antiretroviral therapy.","authors":"Henrique Fernando Lopes-Araujo, Wlisses Henrique Veloso Carvalho-Silva, José Leandro Andrade-Santos, Maria Carolina Santos Guedes, Fabrício Oliveira Souto, Luiz Cláudio Arraes De Alencar, Isadora Bandeira De Luna Paes Barreto Brennand, Thayana Karinne Oliveira Monteiro, Kleyverson Feliciano-Santos, José Artur Bogo Chies, Rafael Lima Guimarães","doi":"10.1007/s00430-026-00872-4","DOIUrl":"10.1007/s00430-026-00872-4","url":null,"abstract":"<p><p>The CCR5Δ32 polymorphism is a 32-base pair deletion in the CCR5 gene that has been associated with slower HIV disease progression. However, its role in immune reconstitution during antiretroviral therapy (ART) remains unclear. We analyzed 236 virologically suppressed people living with HIV (PLHIV) after 24 months of ART, comprising 217 individuals homozygous for the wild-type CCR5 allele and 19 heterozygous carriers of CCR5Δ32. Heterozygotes exhibited a significantly higher frequency of central memory CD4+ T cells compared with wild-type homozygotes (40.33 ± 8.79 vs. 32.71 ± 7.06; p = 0.0196), along with a tendency toward increased effector CD4+ T cells (5.100 [1.818–7.588] vs. 2.260 [1.485–3.503]; p = 0.0459). In contrast, longitudinal follow-up revealed that wild-type homozygotes achieved higher absolute CD4+ T cell counts at both 18 and 24 months of ART (p < 0.05). These results suggest that CCR5Δ32 contributes to qualitative preservation of CD4+ T cell subsets while limiting quantitative immune reconstitution, thereby providing novel insights into the long-term immunological impact of this polymorphism in virologically suppressed PLHIV.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623277","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}
Joana Saraiva, Joana N Bugalhão, Teresa Carvalho, Zach Hensel, Alvaro Crevenna, L Jaime Mota, Irina S Franco
{"title":"The small GTPase Rab5 inhibits actin polymerization mediated by the Legionella pneumophila effector VipA.","authors":"Joana Saraiva, Joana N Bugalhão, Teresa Carvalho, Zach Hensel, Alvaro Crevenna, L Jaime Mota, Irina S Franco","doi":"10.1007/s00430-026-00871-5","DOIUrl":"10.1007/s00430-026-00871-5","url":null,"abstract":"<p><p>Legionella pneumophila is a facultative intracellular bacterium that causes Legionnaires’ disease, one of the most severe manifestations of atypical pneumonia. The capacity of L. pneumophila to cause disease relates with its ability to survive and multiply inside a membrane-bound compartment, the Legionella-containing vacuole (LCV). The remodeling of the LCV into a replication-competent compartment requires the Icm/Dot type 4 secretion system, that translocates over 300 bacterial effector proteins into host cells. Their action is concerted spatially and timely in order to modulate a multitude of host cell targets and thus ensure LCV segregation from the phagolysosomal pathway. The L. pneumophila effector VipA associates with early endosomes and promotes the nucleation of new actin filaments in vitro. Additionally, ectopically produced VipA impairs vesicle trafficking in Saccharomyces cerevisiae. However, the mechanisms underlying its association with the endocytic pathway have remained elusive. In this work, we sought the molecular interacting partners of VipA in early endosomes and explored the effects of this association. We found that VipA interacts directly with two key components of these organelles, the membrane lipid phosphoinositide 3-phosphate (PI3P) and the small GTPase Rab5. Binding to Rab5 requires the NH2-terminal region of VipA but not the COOH-terminal/actin-binding region. Furthermore, binding to Rab5 inhibits VipA-mediated actin polymerization by preventing de novo actin filament formation. These findings offer new insights into the mode of action of VipA and underscore the intricate network of interactions between L. pneumophila effectors and their host cell targets, namely in the endocytic pathway.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13046614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593107","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}
Rima Alsalihi, Kerstin Andersson, Alaitz Aranburu, Christine Lingblom, Linda Wass, Catharina Lewerin, Marie Edvinsson, Andreas Mårtensson, Kenneth Nilsson, Elisabet Skoog, Anna-Carin Lundell, Beatrice Bergström, Anna Grankvist, Christine Wennerås
{"title":"Detection of human antibody responses to tick-borne Neoehrlichia mikurensis.","authors":"Rima Alsalihi, Kerstin Andersson, Alaitz Aranburu, Christine Lingblom, Linda Wass, Catharina Lewerin, Marie Edvinsson, Andreas Mårtensson, Kenneth Nilsson, Elisabet Skoog, Anna-Carin Lundell, Beatrice Bergström, Anna Grankvist, Christine Wennerås","doi":"10.1007/s00430-026-00869-z","DOIUrl":"10.1007/s00430-026-00869-z","url":null,"abstract":"<p><p>Tick-borne Neoehrlichia mikurensis is the cause of neoehrlichiosis, an infectious disease that features fever and vascular events. Compromised B-cell immunity is a risk factor for severe neoehrlichiosis, indicating the importance of antibodies in host defense. The development of serological assays has been hampered by the difficulty of culturing these intracellular bacteria. Here we present the first serological test for N. mikurensis, an ELISA for human IgM and IgG antibody responses to a P44/Msp2 protein of N. mikurensis. Serum or plasma from immunocompetent (n = 44) and immunosuppressed (n = 60) Swedish adults infected with N. mikurensis, with and without symptoms, were analyzed and compared with blood samples from non-infected immunocompetent individuals (n = 17). Sera from non-infected children (n = 23) and plasma from cord blood (n = 10) were also analyzed. Immunocompetent neoehrlichiosis adults had higher IgM and IgG antibody levels compared with immunosuppressed neoehrlichiosis patients treated with the B-cell suppressive agent rituximab. There were no significant differences in the IgM or IgG antibody levels between immunocompetent individuals with symptomatic versus asymptomatic N. mikurensis infection. Sera from healthy children contained high levels of IgM antibodies, despite no evidence of current infection with N. mikurensis nor previous exposure to tick bites as reflected by negative Borrelia serology. This IgM response was absent in cord blood plasma (n = 10), indicating it was not due to natural IgM antibodies. The high constitutional IgM antibody levels to N. mikurensis in children may explain why there have been no reports of pediatric neoehrlichiosis.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444208","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}
Angélica Samer Lallo Dias, Felipe Rocha da Silva Santos, Jenniffer Ramos Martins, Viviane Lima Batista, Talita Cristina Martins da Fonseca, Leticia Pereira Soldati, Celso Martins Queiroz-Junior, Franck Amblard, Raymond F Schinazi, Mauro Martins Teixeira, Vivian Vasconcelos Costa
{"title":"The 2'-α-Fluoro,2'-β-Bromo uridine phosphoramidate prodrug (2-BFU) reduces dengue virus replication and attenuates infection-induced thrombocytopenia In Vivo.","authors":"Angélica Samer Lallo Dias, Felipe Rocha da Silva Santos, Jenniffer Ramos Martins, Viviane Lima Batista, Talita Cristina Martins da Fonseca, Leticia Pereira Soldati, Celso Martins Queiroz-Junior, Franck Amblard, Raymond F Schinazi, Mauro Martins Teixeira, Vivian Vasconcelos Costa","doi":"10.1007/s00430-026-00868-0","DOIUrl":"10.1007/s00430-026-00868-0","url":null,"abstract":"<p><p>Dengue virus (DENV) infection remains a major global health concern, with clinical manifestations ranging from mild febrile illness to severe, life-threatening complications. In the absence of specific antiviral therapies, the development of novel treatment strategies is crucial. This study evaluates the in vivo antiviral efficacy of 2-BFU, a 2′-α-fluoro,2′-β-bromouridine monophosphate prodrug, in a murine model of DENV Serotype 2 (DENV-2) infection. Adult A129 mice were infected subcutaneously with DENV-2 and treated intraperitoneally with 2-BFU at 15 mg/kg, starting 12 h post-infection. Treatment with 2-BFU significantly reduced viral titers in plasma, spleen, and liver, demonstrating potent antiviral activity. Moreover, 2-BFU effectively attenuated DENV-2 -induced thrombocytopenia at 72- and 120-h post-infection. However, the treatment did not significantly affect the production of inflammatory mediators, nor did it prevent infection-associated weight loss or mortality. These findings suggest that 2-BFU holds promise as an antiviral candidate by lowering viral burden and ameliorating thrombocytopenia, although it may require adjunctive anti-inflammatory strategies to improve overall clinical outcomes. Further investigation is warranted to optimize its therapeutic potential for dengue.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12953397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326581","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}
Elsy Martínez-Gorgonio, Rosa Del Carmen Rocha-Gracia, Miguel Castañeda-Lucio, Margarita M P Arenas-Hernández, Miguel A Cevallos, Yolanda Sáenz, Patricia Lozano-Zarain
{"title":"Characterization of outer membrane vesicles from Acinetobacter haemolyticus and their role in the dissemination of carbapenem resistance.","authors":"Elsy Martínez-Gorgonio, Rosa Del Carmen Rocha-Gracia, Miguel Castañeda-Lucio, Margarita M P Arenas-Hernández, Miguel A Cevallos, Yolanda Sáenz, Patricia Lozano-Zarain","doi":"10.1007/s00430-026-00870-6","DOIUrl":"10.1007/s00430-026-00870-6","url":null,"abstract":"<p><p>Species outside the Acinetobacter calcoaceticus–baumannii (Acb) complex have recently emerged as new clinically relevant carbapenem-resistant pathogens, such as A. haemolyticus. A new mechanism that could contribute to the dissemination of this resistance is the secretion of outer membrane vesicles (OMVs). We investigate OMVs secreted by A. haemolyticus AN54, a Mexican clinical strain carrying a plasmid-borne blaNDM−1 gene and by its plasmid-cured derivative AN54Δe. Active secretion of OMVs formed by a lipid membrane, measuring 10–50 nm in both strains, was observed by TEM. The OMVs from AN54 possess hydrolytic capacity against carbapenem. The OMV protein profile varied depending on the antibiotic concentration during induction, with additional protein bands detected at 8 and 32 µg/ml of antibiotic exposure. Mass spectrometry identified proteins involved in different metabolic pathways and in resistance-related processes. The porins, efflux pumps, and ADC enzyme were more abundant in the OMVs from AN54Δe than in those from AN54 harboring the active NDM-1 enzyme. The OMVs protected the sensitive strains from the same and different genera against the antibiotic action for a limited period. However, the OMVs transferred the blaNDM−1-carrying plasmid (pAhaeAN54e) only to the AN54Δe strain, conferring permanent resistance to carbapenems. Together, these findings suggest that OMVs can help protect surrounding bacteria from antibiotic action and serve as vehicles for disseminating resistance genes. These results show the importance of studying OMVs as a novel mechanism for the dissemination of antimicrobial resistance.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147307513","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}
Ting Huang, Siyou Che, Hong Zhang, Wei Jiang, Danrui Hao, Zheng Lv, Yang Yuan, Yundong Zhang, Ruibin Yang, Linqiu Luo, Lufeng Dan, Yiwen Chu, Kelei Zhao, Yanan Shang
{"title":"A potent protein vaccines OmpW induces strong protective immunity against Klebsiella pneumoniae in a mouse model.","authors":"Ting Huang, Siyou Che, Hong Zhang, Wei Jiang, Danrui Hao, Zheng Lv, Yang Yuan, Yundong Zhang, Ruibin Yang, Linqiu Luo, Lufeng Dan, Yiwen Chu, Kelei Zhao, Yanan Shang","doi":"10.1007/s00430-026-00867-1","DOIUrl":"10.1007/s00430-026-00867-1","url":null,"abstract":"<p><p>Klebsiella pneumoniae causes severe respiratory-associated infections in healthy individuals, and widespread antibiotic resistance in K. pneumoniae poses a global health threat. Although great efforts have been taken to develop effective vaccines against K. pneumoniae, there are no licensed vaccines against K. pneumoniae available up to date. In the current study, we designed a potent subunit vaccine OmpW, which was obtained from an outer membrane protein (OmpW) to maximize host responses in mice. Antibody-mediated responses and protective effects were determined to compare the immunogenicity of the OmpW subunit vaccine in the vaccinated mice. Immunization experiments showed that mice immunized with recombinant OmpW generated high IgG antibody production, which promoted macrophage opsonophagocytic activity and induced strong serum bactericidal activity. The residual bacterial burdens from the different organs were declined in the immunized mice compared with the control group. Notably, immunization with the OmpW subunit vaccine provided better protection against K. pneumoniae challenge in vaccinated mice. The passive transfer of antiserum from OmpW-immunized mice also provided protection against K. pneumoniae infection. This study constitutes an important step toward developing potent antibacterial vaccines against K. pneumoniae infections and prevents further dissemination of K. pneumoniae strains.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":"6"},"PeriodicalIF":3.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018900","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}
Jens Magnus Bernth Jensen, Ole Schmeltz Søgaard, Mikkel Steen Petersen, Steen Hoffmann, Bjarne Kuno Møller, Annette Gudmann Hansen, Uffe B Skov Sørensen, Steffen Thiel
{"title":"Isohemagglutinins exhibit synergistic polyreactivity toward Streptococcus pneumoniae surface antigens: implications for broad-spectrum reactivity of human antibodies.","authors":"Jens Magnus Bernth Jensen, Ole Schmeltz Søgaard, Mikkel Steen Petersen, Steen Hoffmann, Bjarne Kuno Møller, Annette Gudmann Hansen, Uffe B Skov Sørensen, Steffen Thiel","doi":"10.1007/s00430-025-00862-y","DOIUrl":"10.1007/s00430-025-00862-y","url":null,"abstract":"<p><p>Synergistic polyreactivity of antibodies—where distinct oligo- or polyreactive clones combine to enable broad-spectrum antigen binding—was recently demonstrated for human anti-galactose-α-1,3-galactose (αGal) antibodies. However, it remains unclear whether this phenomenon also occurs in other antigen-defined antibody populations. Here, we investigated synergistic polyreactivity in isohemagglutinins (naturally occurring antibodies against ABO blood group antigens) and its potential role in antimicrobial defense. Isohemagglutinins were affinity-purified from pooled plasma from groups of healthy donors sharing the same ABO blood group, then characterized by solid-phase immunoassays, SDS-PAGE, and Western blotting. Binding to formaldehyde-fixed Streptococcus pneumoniae representing 30 serotypes was assessed by flow cytometry. Specificity was further examined using inhibition assays with soluble pneumococcal polysaccharides. To evaluate clinical relevance, ABO blood group types (used as proxies for isohemagglutinin profiles) were linked to serotype-specific invasive pneumococcal disease (IPD) events using Danish nationwide registry data. The purified isohemagglutinins retained specificity for their cognate ABO antigens. Notably, they bound all tested pneumococcal strains, primarily through reactivity with the common cell wall polysaccharide. Adsorption studies further revealed serotype-specific capsule binding mediated by distinct isohemagglutinin clones, demonstrating synergistic polyreactivity. Despite this, population-level analyses showed only modest protection: most notably, individuals with blood types B or O (producers of anti-A and anti-A,B isohemagglutinins, respectively) had a 19% lower prevalence of serotype 9V IPD than blood type A or AB individuals. Although the overall protective effect of isohemagglutinins against IPD seems limited, the observed synergistic polyreactivity supports the concept that this is a general feature of antigen-defined antibodies, extending beyond anti-αGal antibodies.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":"5"},"PeriodicalIF":3.1,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12789223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145944694","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":"A novel TamA + LtgC bivalent vaccine induces potent immunogenic and bactericidal antibodies against Neisseria gonorrhoeae.","authors":"Narjes Noori Goodarzi, Soheila Ajdary, Mahdi Torkamaneh, Farzaneh Aminharati, Mohammad Reza Pourmand, Farzad Badmasti","doi":"10.1007/s00430-025-00866-8","DOIUrl":"10.1007/s00430-025-00866-8","url":null,"abstract":"<p><p>Development of an effective vaccine against Neisseria gonorrhoeae comes with unique challenges. After five decades of research, the lack of an FDA-approved vaccine underscores the need for novel immunization strategies. Therefore, in this study, we evaluated a bivalent vaccine compared to two single-antigen formulations containing LtgC or TamA. The tamA and ltgC genes were cloned, expressed and purified. Serum IgG levels against recombinant proteins in gonorrhea patients were assessed by the enzyme-linked immunosorbent assay (ELISA). Mice were immunized with TamA and/or LtgC formulations alongside Monophosphoryl-lipid A (MPLA) adjuvant. Serum and vaginal IgG and IgA levels were measured. Then, the serum bactericidal assay (SBA), and opsonophagocytic activity (OPA) assays were performed. The presence of antigen-specific antibodies in patients’ sera indicates that the recombinant proteins elicit immune responses in natural infection. All formulations elicited robust long-lasting systemic IgG responses, with TamA + MPLA inducing the highest IgG titers. The bivalent formulation showed superior IgA responses in serum, while in vaginal wash, its superiority was not evident. TamA + MPLA and the bivalent formulation showed comparable higher SBA and OPA titers compared to the LtgC + MPLA. TamA and LtgC monovalent formulations induced long-lasting antibodies, with desirable bactericidal effects. TamA + MPLA and the combination group exhibited similar SBA and OPA titers. Despite the half-dose of TamA in the combination, inclusion of LtgC appears to enhance serum bactericidal activity. Thus, future investigations should focus on dose optimization to maximize synergistic effects of the bivalent formulation.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":"4"},"PeriodicalIF":3.1,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850368","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}
Nina Boeck, Philipp Grubwieser, Rudolf Glueckert, Erika Kvalem Soto, Thomas Sonnweber, Alexander Hoffmann, Richard Hilbe, Stefanie Dichtl, Wilfried Posch, Manfred Nairz, Igor Theurl, Zlatko Trajanoski, Guenter Weiss
{"title":"The role of ciliary function in airway epithelial defense against Pseudomonas aeruginosa.","authors":"Nina Boeck, Philipp Grubwieser, Rudolf Glueckert, Erika Kvalem Soto, Thomas Sonnweber, Alexander Hoffmann, Richard Hilbe, Stefanie Dichtl, Wilfried Posch, Manfred Nairz, Igor Theurl, Zlatko Trajanoski, Guenter Weiss","doi":"10.1007/s00430-025-00865-9","DOIUrl":"10.1007/s00430-025-00865-9","url":null,"abstract":"<p><p>Respiratory cilia play a crucial role in clearing pathogens from the airway, and understanding how Pseudomonas aeruginosa (PA) impairs their function is essential for developing targeted therapies to enhance airway epithelial defense and hamper bacterial invasion. Thus, we investigated the mechanisms by which PA impairs respiratory cilia function and identified pharmacological interventions to restore cilia motility. We used mucociliary differentiated human airway organoids expressing motile cilia on the apical side, to model the initial stage of PA infection. We show that co-culturing of organoids with PA down-regulates the expression of genes associated with cilia formation, structure and function. Electron microscopy confirmed ciliary structural damage and membrane disruption in infected organoids and slowed ciliary beating frequency as quantified by slow-motion video recording. Reduction of cilia function resulted in increased bacterial cell invasion, and we identified the bacterial toxin Pyocyanin as one causative cilia damaging factor. We could further demonstrate, that the selective phosphodiesterase-4 inhibitor Roflumilast can maintain ciliary function and beating frequency upon infection of organoids with PA, thereby reducing bacterial invasion of epithelia in our model system. Our findings emphasize the critical role of motile cilia in innate host defense against PA infection, implying that treatment strategies aimed at restoring ciliary function can enhance epithelial robustness during bacterial invasion. Our human organoid infection model enables the evaluation of cellular and functional responses of the airway epithelium to respiratory pathogens and to test potential therapeutic strategies aimed at restoring ciliary function and improving infection control.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":"3"},"PeriodicalIF":3.1,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12743103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834467","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}
Amirreza Javadi Mamaghani, Maryam Karimi, Ali Haghighi, Seyyed Javad Seyyed Tabaei, Omid Ali Adeli, Somayeh Aghamolaei, Maryam Ebrahimi, Shirzad Fallahi, Ali Mirzapour, Mohammad Yarahmadi
{"title":"A comprehensive multi-epitope recombinant protein strategy for accurate serological detection of Toxoplasma gondii infection.","authors":"Amirreza Javadi Mamaghani, Maryam Karimi, Ali Haghighi, Seyyed Javad Seyyed Tabaei, Omid Ali Adeli, Somayeh Aghamolaei, Maryam Ebrahimi, Shirzad Fallahi, Ali Mirzapour, Mohammad Yarahmadi","doi":"10.1007/s00430-025-00863-x","DOIUrl":"10.1007/s00430-025-00863-x","url":null,"abstract":"<p><p>Toxoplasma gondii is a globally prevalent zoonotic parasite responsible for toxoplasmosis. Accurate serological diagnosis remains challenging due to the lack of standardized, high-performance antigens. In this study, we designed a recombinant multi-epitope protein (ME-TG) by selecting B-cell epitopes from four immunodominant antigens: SAG1, GRA7, GRA4, and GRA14. The ME-TG construct was expressed in E. coli, purified, and evaluated using ELISA across 189 serum samples, including acute (n = 45), chronic (n = 38), healthy controls (n = 62), and individuals with other parasitic or bacterial infections (n = 42). The ME-TG-based ELISA demonstrated 98% sensitivity for both IgG and IgM detection, and 100% specificity, with no observed cross-reactivity. These findings highlight the diagnostic potential of ME-TG as a standardized serological marker for human toxoplasmosis. Further validation using larger, geographically diverse cohorts and additional T. gondii antigens is recommended to enhance clinical applicability.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"215 1","pages":"2"},"PeriodicalIF":3.1,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804933","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}