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Tackling cutaneous herpes simplex virus disease with topical immunomodulators—a call to action
(American Society for Microbiology, 2025-03-13)
DUARTE PEÑALOZA, LUISA FERNANDA
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Javier Carbone-Schellman
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Susan M. Bueno
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Alexis M. Kalergis
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Claudia A. Riedel
Antivirals play important roles in restricting viral diseases. Nevertheless, they act on a relatively limited number of viruses and occasionally display partial effectiveness in some tissues or against escape variants. Although vaccination remains the most cost-effective approach for preventing microbial diseases, developing prophylactic or therapeutic solutions for pathogens, such as herpes simplex viruses (HSVs), that effectively reduce their clinical manifestations in the skin has proven exceptionally challenging despite extensive research. Alternatively, a less explored approach for tackling HSV skin infection involves using topical immunomodulatory molecules to potentiate the host’s innate antiviral immune responses. When applied directly to herpetic skin lesions where viral antigen is present, this strategy has the potential to elicit virus-specific adaptive immunity. Based on currently available data, we foresee substantial potential for this approach in addressing HSV skin infections, along with additional prospects to advance understanding of skin biology and apply relevant new findings to other dermatological conditions. However, due to the limited number of case studies evaluating this method and its safety profile, particularly in immunocompromised individuals and pregnant women, further research is crucial, especially to assess the effects of immunomodulators in these vulnerable populations. Here, we revisit and discuss the use of immunomodulatory molecules for potentiating the host immune response against HSV skin infection and call for action for increased research and clinical trials regarding the possible benefits of this latter strategy for treating HSV cutaneous disease and recurrences. We also revisit and discuss antivirals and vaccine candidates against HSVs.
Scopus© Citations 2 7
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IL-10 and IL-6/IL-10 as predictive biomarkers for treatment response in non-infectious uveitis
(Frontiers Media SA, 2025-05-13)
Rodrigo A. Valenzuela
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Fabian Vega-Tapia
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Nathaly Elizalde
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Ivan Flores
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Felipe M. Rojas
Uveitis, a group of heterogeneous diseases causing ocular inflammation, is a major contributor to vision loss globally. While systemic corticosteroids (CS) are the mainstay treatment, identifying CS-refractory patients remains a significant challenge. This study aimed to explore cytokine expression and Glucocorticoid Receptor (GR) levels as biomarkers for the early detection of CS-refractory cases in non-infectious uveitis. We assayed blood samples from 19 patients with non-infectious uveitis, for the expression of IL-6, IL-17A, TNF-α, IL-10 and GRα. The cohort included 11 refractory and 8 sensitive patients, categorized based on their clinical response to corticosteroids (prednisone 1 mg/kg/day). Blood draws were conducted at three time points (at baseline, day 7- and day 14 after CS initiation), and peripheral blood mononuclear cells (PBMCs) were isolated to measure cytokine and GRα transcript levels via real-time PCR. The expression levels of GRα and cytokines IL-6, IL-17A and TNF-α did not show significant changes between CS-sensitive and CS-refractory patients on the different days of treatment. However, IL-10 expression levels as the day14-to-day7 ratio were significantly higher in patients sensitive to CS therapy. A higher day14-to-day7 ratio was also found for the IL-6/IL-10, IL-17A/IL-10 and GRα/IL-10 ratios. ROC curve analysis demonstrated a robust predictive performance of IL-10 mRNA expression and the IL-6/IL-10 ratio for identifying CS-refractory patients. In conclusion, the expression of IL-10 and the IL-6/IL-10 ratio hold promise as early predictive biomarkers for CS treatment refractoriness in patients with non-infectious uveitis. These findings offer valuable insights into personalized treatment strategies, potentially leading to improved clinical outcomes.
Scopus© Citations 6 1
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TGFβ links EBV to multisystem inflammatory syndrome in children
(Springer Science and Business Media LLC, 2025-03-12)
Carl Christoph Goetzke
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Mona Massoud
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Stefan Frischbutter
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Gabriela Maria Guerra
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Marta Ferreira-Gomes
<jats:title>Abstract</jats:title> <jats:p>In a subset of children and adolescents, SARS-CoV-2 infection induces a severe acute hyperinflammatory shock<jats:sup>1</jats:sup> termed multisystem inflammatory syndrome in children (MIS-C) at four to eight weeks after infection. MIS-C is characterized by a specific T cell expansion<jats:sup>2</jats:sup> and systemic hyperinflammation<jats:sup>3</jats:sup>. The pathogenesis of MIS-C remains largely unknown. Here we show that acute MIS-C is characterized by impaired reactivation of virus-reactive memory T cells, which depends on increased serum levels of the cytokine TGFβ resembling those that occur during severe COVID-19 (refs. <jats:sup>4,5</jats:sup>). This functional impairment in T cell reactivity is accompanied by the presence of TGFβ-response signatures in T cells, B cells and monocytes along with reduced antigen-presentation capabilities of monocytes, and can be reversed by blocking TGFβ. Furthermore, T cell receptor repertoires of patients with MIS-C exhibit expansion of T cells expressing TCRVβ21.3, resembling Epstein–Barr virus (EBV)-reactive T cell clones capable of eliminating EBV-infected B cells. Additionally, serum TGFβ in patients with MIS-C can trigger EBV reactivation, which is reversible with TGFβ blockade. Clinically, the TGFβ-induced defect in T cell reactivity correlates with a higher EBV seroprevalence in patients with MIS-C compared with age-matched controls, along with the occurrence of EBV reactivation. Our findings establish a connection between SARS-CoV-2 infection and COVID-19 sequelae in children, in which impaired T cell cytotoxicity triggered by TGFβ overproduction leads to EBV reactivation and subsequent hyperinflammation.</jats:p>
Scopus© Citations 4 2
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Population-based seroprevalence survey: post-pandemic COVID-19 vaccination, related factors, and geographic distribution of vaccine acceptability in Chile
(Springer Science and Business Media LLC, 2025-03-28)
Loreto Nuñez-Franz
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RUBILAR RAMIREZ, PAOLA ANDREA
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APABLAZA SALINAS, MAURICIO IVÁN
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Luis Canales
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CORTES SALINAS, LINA JIMENA
10
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Clinical, immunologic, and genetic characteristics of 148 patients with natural killer cell deficiency
(Elsevier BV, 2025-05)
Manar Abdalgani
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Evelyn R. Hernandez
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Luis A. Pedroza
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Ivan K. Chinn
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Lisa R. Forbes Satter
Scopus© Citations 1 2
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Immunogenicity of the 9-valent human papillomavirus vaccine: Post hoc analysis from five phase 3 studies
(Informa UK Limited, 2025-01-22)
Anna R. Giuliano
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Joel M. Palefsky
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Stephen E. Goldstone
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Jacob Bornstein
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Ilse De Coster
Scopus© Citations 8 2
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Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature
(American Association for the Advancement of Science (AAAS), 2025-01-10)
Marita Bosticardo
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Kerry Dobbs
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Ottavia M. Delmonte
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Andrew J. Martins
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Francesca Pala
<jats:p> Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of <jats:italic>RAG</jats:italic> -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic <jats:italic>RAG</jats:italic> variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons. T helper 2 (T <jats:sub>H</jats:sub> 2) cell skewing and a prominent inflammatory signature characterize Omenn syndrome, whereas more hypomorphic forms of RAG deficiency are associated with a type 1 immune profile both in blood and tissues. We used cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) analysis to define the cell lineage–specific contribution to the immunopathology of the distinct RAG phenotypes. These insights may help improve the diagnosis and clinical management of the various forms of the disease. </jats:p>
Scopus© Citations 2 1
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Neonatal Mesenchymal Stem Cell Treatment Improves Myelination Impaired by Global Perinatal Asphyxia in Rats
(2021)
Andrea Tapia-Bustos
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Carolyne Lespay-Rebolledo
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Valentina Vío
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Ronald Pérez-Lobos
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Emmanuel Casanova-Ortiz
<jats:p>The effect of perinatal asphyxia (PA) on oligodendrocyte (OL), neuroinflammation, and cell viability was evaluated in telencephalon of rats at postnatal day (P)1, 7, and 14, a period characterized by a spur of neuronal networking, evaluating the effect of mesenchymal stem cell (MSCs)-treatment. The issue was investigated with a rat model of global PA, mimicking a clinical risk occurring under labor. PA was induced by immersing fetus-containing uterine horns into a water bath for 21 min (AS), using sibling-caesarean-delivered fetuses (CS) as controls. Two hours after delivery, AS and CS neonates were injected with either 5 μL of vehicle (10% plasma) or 5 × 104 MSCs into the lateral ventricle. Samples were assayed for myelin-basic protein (MBP) levels; Olig-1/Olig-2 transcriptional factors; Gglial phenotype; neuroinflammation, and delayed cell death. The main effects were observed at P7, including: (i) A decrease of MBP-immunoreactivity in external capsule, corpus callosum, cingulum, but not in fimbriae of hippocampus; (ii) an increase of Olig-1-mRNA levels; (iii) an increase of IL-6-mRNA, but not in protein levels; (iv) an increase in cell death, including OLs; and (v) MSCs treatment prevented the effect of PA on myelination, OLs number, and cell death. The present findings show that PA induces regional- and developmental-dependent changes on myelination and OLs maturation. Neonatal MSCs treatment improves survival of mature OLs and myelination in telencephalic white matter.</jats:p>
Scopus© Citations 7 2
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Major Histocompatibility Complex Class I-Related Chain A (MICA) Allelic Variants Associate With Susceptibility and Prognosis of Gastric Cancer
(2021)
Karen Toledo-Stuardo
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Carolina H. Ribeiro
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Andrea Canals
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Marcela Morales
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Valentina Gárate
<jats:p>Gastric cancer (GC) is the fifth most prevalent type of cancer worldwide. Gastric tumor cells express MICA protein, a ligand to NKG2D receptor that triggers natural killer (NK) cells effector functions for early tumor elimination. <jats:italic>MICA</jats:italic> gene is highly polymorphic, thus originating alleles that encode protein variants with a controversial role in cancer. The main goal of this work was to study <jats:italic>MICA</jats:italic> gene polymorphisms and their relationship with the susceptibility and prognosis of GC. Fifty patients with GC and 50 healthy volunteers were included in this study. MICA alleles were identified using Sanger sequencing methods. The analysis of <jats:italic>MICA</jats:italic> gene sequence revealed 13 MICA sequences and 5 MICA-short tandem repeats (STR) alleles in the studied cohorts We identified MICA<jats:sup>*</jats:sup>002 (<jats:sup>*</jats:sup>A9) as the most frequent allele in both, patients and controls, followed by MICA<jats:sup>*</jats:sup>008 allele (<jats:sup>*</jats:sup>A5.1). MICA<jats:sup>*</jats:sup>009/049 allele was significantly associated with increased risk of GC (OR: 5.11 [95% CI: 1.39–18.74], <jats:italic>p</jats:italic> = 0.014). The analysis of MICA-STR alleles revealed a higher frequency of MICA<jats:sup>*</jats:sup>A5 in healthy individuals than GC patients (OR = 0.34 [95% CI: 0.12–0.98], <jats:italic>p</jats:italic> = 0.046). Survival analysis after gastrectomy showed that patients with MICA<jats:sup>*</jats:sup>002/002 or MICA<jats:sup>*</jats:sup>002/004 alleles had significantly higher survival rates than those patients bearing MICA<jats:sup>*</jats:sup>002/008 (<jats:italic>p</jats:italic> = 0.014) or MICA<jats:sup>*</jats:sup>002/009 (MICA<jats:sup>*</jats:sup>002/049) alleles (<jats:italic>p</jats:italic> = 0.040). The presence of threonine in the position MICA-181 (MICA<jats:sup>*</jats:sup>009/049 allele) was more frequent in GC patients than controls (<jats:italic>p</jats:italic> = 0.023). Molecular analysis of MICA-181 showed that the presence of threonine provides greater mobility to the protein than arginine in the same position (MICA<jats:sup>*</jats:sup>004), which could explain, at least in part, some immune evasion mechanisms developed by the tumor. In conclusion, our findings suggest that the study of MICA alleles is crucial to search for new therapeutic approaches and may be useful for the evaluation of risk and prognosis of GC and personalized therapy.</jats:p>
Scopus© Citations 12 1
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Broad and potently neutralizing monoclonal antibodies isolated from human survivors of New World hantavirus infection
(2021)
Taylor B. Engdahl
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Natalia A. Kuzmina
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Adam J. Ronk
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Chad E. Mire
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Matthew A. Hyde
Scopus© Citations 23 2

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