ImmunoHorizons最新文献

{"title":"Giardia increases macrophage production of the anti-inflammatory cytokine interleukin-10 in response to lipopolysaccharide via macrophage galactose binding lectin.","authors":"Vanessa V Angelova, Rita T Kosile, Matthew Darmadi, Eleanor G Miskovsky, Marc Y Fink, Samantha Menegas, Haley Wexelblatt, Steven M Singer","doi":"10.1093/immhor/vlaf019","DOIUrl":"10.1093/immhor/vlaf019","url":null,"abstract":"<p><p>Giardia duodenalis is an intestinal protozoan parasite common in low- and middle-income countries. Infection is often subclinical, even when it is associated with other pathologies like growth stunting in children. Recent longitudinal cohort studies have found Giardia more frequently in patients with milder symptoms and have even suggested that Giardia reduces rotavirus symptom severity. One potential mechanism for limiting disease severity due to other enteropathogens is the promotion of anti-inflammatory responses that limit pathology. Our lab previously showed that Giardia reduces production of interleukin (IL)-12 by dendritic cells stimulated with Toll-like receptor agonists. In this study, we show that Giardia increases the production of the anti-inflammatory cytokine IL-10 by mouse peritoneal macrophages in response to bacterial lipopolysaccharide. This potentiation is specific to IL-10, as no changes were seen in the production of the proinflammatory cytokine tumor necrosis factor ɑ. Moreover, peritoneal macrophages from mice lacking macrophage galactose-binding lectin, a pathogen recognition receptor that has been previously shown to bind N-acetylgalactosamine, failed to increase IL-10 production after stimulation with Giardia and lipopolysaccharide. Giardia's immunoregulation of the IL-10 response may help us understand the parasite's role in reducing diarrheal severity.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of pathogenic involvement of CCL4 and its receptor CCR5 in arthritogenic alphavirus disease.","authors":"Muddassar Hameed, Norman A Solomon, James Weger-Lucarelli","doi":"10.1093/immhor/vlaf022","DOIUrl":"10.1093/immhor/vlaf022","url":null,"abstract":"<p><p>Arthritogenic alphaviruses, including chikungunya (CHIKV), Mayaro (MAYV), Ross River (RRV), and O'nyong nyong virus (ONNV), are emerging and reemerging viruses that cause disease characterized by fever, rash, and incapacitating muscle and joint pain and inflammation. Alphavirus infection induces robust immune responses, leading to the upregulation of several cytokines and chemokines, including chemokine C ligand 4 (CCL4). CCL4 is a chemoattractant for immune cells such as T cells, natural killer cells, monocytes/macrophages, and dendritic cells, recruiting these cells to the site of infection, stimulating the release of proinflammatory mediators, and inducing T cell differentiation. CCL4 has been found at high levels in both the acute and chronic phases of chikungunya disease; however, the role of CCL4 in arthritogenic alphavirus disease development remains unexplored. Here, we tested the effect of CCL4 on MAYV infection in mice through antibody neutralization and treatment with recombinant mouse CCL4. We observed no differences in mice depleted of CCL4 or treated with recombinant CCL4 in terms of disease progression such as weight loss and footpad swelling or the development of viremia. CCL4 uses the G protein-coupled receptor C-C chemokine receptor type 5 (CCR5). To determine whether CCR5 deficiency would alter disease outcomes or virus replication in mice, we inoculated CCR5 knockout (CCR5--) mice with MAYV and observed no effect on disease development and immune cell profile of blood and footpads between CCR5-/- and wild type mice. These studies failed to identify a clear role for CCL4 or its receptor CCR5 in MAYV infection.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12137896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of acalabrutinib with best supportive care versus best supportive care in patients with COVID-19 requiring hospitalization.","authors":"Phillip Scheinberg, Matt R Khoshnevis, Philip A Robinson, Alfredo Guerreros, Victor A H Sato, Benedito A L Fonseca, Hans W Prozesky, José Omar Chacón Romero, Laura Fogliatto, Barry R Meisenberg, David J Park, Ashok Gupta, Priti Patel, Danielle M Townsley, Lianqing Zheng, Veerendra Munugalavadla","doi":"10.1093/immhor/vlaf023","DOIUrl":"10.1093/immhor/vlaf023","url":null,"abstract":"<p><p>The efficacy and safety of acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, was evaluated in 2 phase 2 studies in hospitalized patients with coronavirus disease 2019 (COVID-19) who received acalabrutinib + best supportive care (BSC) versus BSC alone (Clinicaltrials.gov: NCT04380688 and NCT04346199). The primary endpoint was the percentage of patients alive and free of respiratory failure on day 14 (rest of the world [RoW] study) and day 28 (US study). In the RoW study, 177 patients were randomized (acalabrutinib + BSC: n = 89; BSC: n = 88); in the US study, 62 patients were randomized (acalabrutinib + BSC: n = 31; BSC: n = 31). The percentage of patients who met the primary endpoint was similar in both studies (RoW study: acalabrutinib + BSC: 83.1%, BSC: 90.9%; US study: acalabrutinib + BSC: 80.6%, BSC: 83.9%). No new safety concerns were reported. Overall, no significant clinical benefit of adding acalabrutinib to BSC in patients hospitalized with COVID-19 was observed.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of IgE cross-reactivity and allergenicity of peanut allergens.","authors":"Christian Lapitan, William R Zhang, Beichu Guo, Tracy R Daniels-Wells, Manuel L Penichet, Ke Zhang","doi":"10.1093/immhor/vlaf018","DOIUrl":"10.1093/immhor/vlaf018","url":null,"abstract":"<p><p>IgE cross-reactivity among peanut allergens is controversial, and allergenicity of peanut allergens other than Arachis hypogaea 2 [Ara h 2] remains to be elucidated. We investigated the origins of peanut IgE cross-reactivity using Western blotting, and allergenicity of peanut allergens employing a passive cutaneous anaphylaxis model. Peanut allergic IgE bound to a large swath of peanut proteins including Ara h 2, Ara h 1, Ara h 3, and Ara h 6. IgE cross-reactivity among peanut allergens could be inhibited by recombinant Ara h 2. Affinity-purified Ara h 2 IgE reconstituted broad IgE binding patterns to Ara h 1, Ara h 3, and Ara h 6 in addition to Ara h 2. Monoclonal human IgE and mouse IgG against peanut allergen component variably bound to other peanut allergen components. Ara h 2 and Ara h 6 could trigger Ara h 2 IgE-mediated peanut allergic reactivity, whereas Ara h 1 and Ara h 3 failed to do so. Ara h 1 IgE was incapable of mediating Ara h 1-triggered allergic reaction. These results revealed that Ara h 2 IgE was the origin of IgE cross-reactivity, and Ara h 2 IgE-mediated peanut allergic reactivity triggered by Ara h 2 and Ara h 6. Ara h 1 and Ara h 3 did not display detectable allergenicity. These results indicated that Ara h 2 IgE appeared to be the \"master\" responsible for IgE cross-reactivity among peanut allergens and might be the only IgE responsible for allergic reactivity in peanut allergy.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imprints of somatic hypermutation on B-cell receptor immunoglobulins post-infection versus post-vaccination against SARS-CoV-2.","authors":"Elisavet Vlachonikola, Nikolaos Pechlivanis, Georgios Karakatsoulis, Massimo Degano, Fotis Psomopoulos, Andrea Crisanti, Giovanni Tonon, Paolo Ghia, Kostas Stamatopoulos, Enrico Lavezzo, Anastasia Chatzidimitriou","doi":"10.1093/immhor/vlaf021","DOIUrl":"10.1093/immhor/vlaf021","url":null,"abstract":"<p><p>Published evidence supports significant heterogeneity of immune responses among individuals infected with or vaccinated against SARS-CoV-2. This highlights the need for in-depth investigation of the implicated processes toward refined understanding and improved management of COVID-19. The main objective of the present study was to investigate the dynamics of B cell responses to SARS-CoV-2, focusing on how initial infection and subsequent vaccination influence the immunoglobulin gene repertoire, with special emphasis on the impact of somatic hypermutation (SHM) on antibody maturation. Samples were collected from 81 individuals infected by SARS-CoV-2 in the municipality of Vo' during the first pandemic wave in 2020. For 25 of them, sampling was repeated 7 d after completing the primary vaccination series. Deep immunogenetic analysis of the B-cell receptor immunoglobulin (BcR IG) gene repertoire was performed using targeted next-generation sequencing. Bioinformatics analysis focused on repertoire metrics, prediction of IG antigen specificity, and detailed profiling of the SHM patterns. Significant expansions of unmutated sequences early post-infection suggest extrafollicular B cell maturation. In contrast, vaccination promoted SHM acquisition, indicating a germinal center-dependent response, and pronounced repertoire renewal. Restricted SHMs in SARS-homologous clonotypes along with preferential targeting of specific codons within the VH domain post-vaccination support ongoing affinity maturation within germinal centers. Differences in the BcR IG profiles post-infection versus post-vaccination allude to distinct trajectories in B cell maturation. Distinct profiles of SHM targeting reflect ongoing affinity maturation post-vaccination, with implications for optimizing preventive and therapeutic interventions against COVID-19.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of tissue resident memory T cells in malignant pleural effusions associated with non-small cell lung cancer.","authors":"Caitlin M Tilsed, Joshua Brotman, Shaun O'Brien, Brennan Lee, Edmund Moon, Steven M Albelda","doi":"10.1093/immhor/vlaf013","DOIUrl":"https://doi.org/10.1093/immhor/vlaf013","url":null,"abstract":"<p><p>Tissue resident memory T cells (TRM) play a critical role in cancer immunity and their presence in solid tumors is associated with improved prognosis and response to therapy. Although TRM have been identified and their function characterized in lung cancers, little is known regarding TRM outside of a tissue context, such as within malignant pleural effusions (MPE). As MPE are routinely drained and collected to manage symptoms, analysis of this fluid can provide an insight into the peri-tumoral environment. In this study, we performed flow cytometry and single cell RNAseq (scRNAseq) on MPE associated with non-small lung cancer and examined the phenotype and function of TRM. We found that 14% of CD8+ T cells and 6% of CD4+ T cells were TRM, as defined by the phenotype of CD45RO+CCR7-CD62L- and expressing 1 or both of CD69 and CD103. The scRNAseq revealed distinct clusters expressing TRM-associated genes including ITGAE and CD49A and lacking expression of SELL, CCR7, and IL7RA. TRM did not differ from other memory T cell subsets, such as T central memory (TCM) and T effector memory (TEM) cells, in expression of the inhibitory markers PD-1, TIGIT, and CD39. When TRM function was assessed by measuring the production of IFN-γ, TNF-α, and CD107a after stimulation with αnti-CD3 antibodies in vitro, TRM had comparable function to T effector cells (TE), indicating that despite expression of exhaustion markers these cells retained effector function. Finally, we found that CD69 expression, and not CD103 expression, on TRM was associated with production of effector cytokines.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAP-1-derived peptide suppresses TCR-mediated T cell activation and ameliorates immune diseases by inhibiting STAP-1-LCK binding.","authors":"Yuto Sasaki, Kota Kagohashi, Shoya Kawahara, Yuichi Kitai, Ryuta Muromoto, Kenji Oritani, Jun-Ichi Kashiwakura, Tadashi Matsuda","doi":"10.1093/immhor/vlaf015","DOIUrl":"https://doi.org/10.1093/immhor/vlaf015","url":null,"abstract":"<p><p>Signal-transducing adaptor protein-1 (STAP-1) is an adaptor protein specifically expressed in immune cells, such as T cells. We previously demonstrated that STAP-1 positively upregulates T cell receptor (TCR)-mediated T cell activation by interacting with LCK and phospholipase C-γ1 and affecting autoimmune demyelination and airway inflammation. In this study, we aimed to generate a new STAP-1-derived peptide, iSP1, to inhibit the STAP-1-LCK interaction. We also analyzed its function in vitro and in vivo. iSP1 successfully interfered with STAP-1-LCK binding and suppressed TCR-mediated signal transduction, interleukin-2 production, and human and murine T cell proliferation. Additionally, iSP1 prevented the progression of experimental autoimmune encephalomyelitis by inhibiting Th1 and Th17 cell infiltration. Our findings suggest iSP1 as a new therapeutic immunomodulatory agent for T cell-mediated autoimmune diseases.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing TLR4 agonist EmT4™ as an anti-Mycobacterium tuberculosis vaccine adjuvant.","authors":"Sasha E Larsen, Maham Rais, Valerie A Reese, Debora Ferede, Tiffany Pecor, Suhavi Kaur, Deepika Nag, Thomas Smytheman, Sean A Gray, Darrick Carter, Susan L Baldwin, Rhea N Coler","doi":"10.1093/immhor/vlaf014","DOIUrl":"https://doi.org/10.1093/immhor/vlaf014","url":null,"abstract":"<p><p>Tuberculosis (TB) is again the deadliest infectious disease globally, and more efficacious vaccines are needed to reduce this mortality. Successful subunit TB vaccines need antigens and adjuvants that are immunogenic, inexpensive, and accessible. Here we evaluated the potential of synthetically produced Monophosphoryl lipid A (SyMLP), a TLR4-agonist, formulated in an oil-in-water emulsion (EmT4™) in combination with selected fusion proteins, to drive an effective vaccine-mediated immunogenic response in C57BL/6 mice against Mycobacterium tuberculosis (M.tb) HN878 and H37Rv challenge. We first observed that EmT4™ enhances activation of C57BL/6 bone-marrow derived macrophages and dendritic cells measured by CD40, CD86, and MHCII expression by flow cytometry. EmT4™ did not induce safety signals in a scaled tolerability study. In immunogenicity studies, mice immunized 3 times 3 weeks apart with ID93 antigen + EmT4™ produced a significantly higher magnitude of circulating proinflammatory cytokines and ID93-specific immunoglobulin G (IgG) antibodies pre- and post-challenge with M.tb than saline control animals. Ex vivo ID93 restimulated splenocytes and lung cells elicited significant polyfunctional CD4+ T-helper 1 responses. Importantly, ID93 + EmT4™ immunizations significantly reduced bacterial burden in C57BL/6 mice 4 weeks post-challenge. Interestingly, EmT4™ paired with a next generation protein fusion ID91 also afforded prophylactic protection against M.tb HN878 challenge in both young (6 to 8 wk) and aged (20 mo) immunocompromised Beige mice. These protection and immunogenicity findings suggest that synthetically derived EmT4™ adjuvant is not only suitable to help backfill the preclinical TB vaccine candidate pipeline but is also suitable for the needs of the global community.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Comprehensive immune profiling of dengue and chikungunya viral responses using a novel miniaturized automated whole blood cellular analysis system and mass cytometry in a pediatric cohort in Msambweni, Kenya.","authors":"","doi":"10.1093/immhor/vlaf020","DOIUrl":"https://doi.org/10.1093/immhor/vlaf020","url":null,"abstract":"","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamics of antimicrobial proteins' expression and their bactericidal activity in mouse milk.","authors":"Piu Saha, Ahmed Abokor, Matam Vijay-Kumar","doi":"10.1093/immhor/vlaf017","DOIUrl":"https://doi.org/10.1093/immhor/vlaf017","url":null,"abstract":"<p><p>Mother's milk is considered as \"complete edible immune system.\" It contains macro- and micronutrients required to maintain infant growth and provides an excellent source for innate and adaptive immune proteins that not only protects infants from enteropathogens but also aid in the initial colonization of gut microbiota. In this study, we analyzed the milk of C57BL/6J dams and found significant changes in the composition of antimicrobial and immune proteins throughout the lactation period. Innate immune proteins, serum amyloid A, soluble CD14, and notably lipocalin-2 were detected in milk at high quantities. These proteins were substantially reduced in the milk from MyD88-deficient dams. Further, adaptive immune proteins, specifically IgA and IgG, exhibit a distinct shift during postpartum lactation stages. While IgG is the dominant immunoglobulin in milk at day 5 postpartum, by day 15 its levels were surpassed by IgA whose levels increased over time. The administration of TLR4 ligand LPS to WT dams significantly increased the aforementioned milk innate and adaptive proteins. Surprisingly, the milk from WT dams suppressed E. coli growth more effectively than milk collected from LPS-treated mice; such suppression, however, was completely lost upon boiling. Intriguingly, IgA, but not Lcn2, serves as a predominant factor in inhibiting E. coli proliferation, suggesting the critical role of IgA in regulating microbial colonization in the neonatal gut. Collectively, our findings provide insight into the dynamics of various immune proteins present in breast milk and highlight their pivotal roles in determining neonatal immune responses and microbial colonization at early stage.</p>","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}