Accelerated T-Cell Immunosenescence in Cytomegalovirus-Seropositive Individuals After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Cytomegalovirus (CMV) infection is a major driver of accelerated immunosenescence related to CD28null T cell expansion. CMV infection and these proatherogenic T cells have been independently associated with cardiovascular disease and coronavirus disease 2019 (COVID-19) severity. We investigated the potential contribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to immunosenescence and its relationship with CMV. Innate and adaptive immune subpopulations from individuals with mild or asymptomatic SARS-CoV-2 infection (mCOVID-19) and healthy donors were immunophenotyped. A significant increase in CD28nullCD57+CX3CR1+ T cell percentages (CD4+ [P ≤ .01], CD8+ [P ≤ .01], and TcRγδ (CD4-CD8-) [P ≤ .001]) was found in unnvaccinated CMV-seropositive mCOVID-19 individuals stable up to 12 months after infection. This expansion did not occur in CMV-seronegative mCOVID-19 individuals or in CMV-seropositive individuals infected after SARS-CoV-2 vaccination. There were no significant differences between mCOVID-19 and aortic stenosis groups. Thus, individuals coinfected with SARS-CoV-2 and CMV have accelerated T cell senescence, which might lead to an increased risk of cardiovascular disease.

A Straightforward Cytometry-Based Protocol for the Comprehensive Analysis of the Inflammatory Valve Infiltrate in Aortic Stenosis.

Aortic stenosis (AS) is a frequent cardiac disease in old individuals, characterized by valvular calcification, fibrosis, and inflammation. Recent studies suggest that AS is an active inflammatory atherosclerotic-like process. Particularly, it has been suggested that several immune cell types, present in the valve infiltrate, contribute to its degeneration and to the progression toward stenosis. Furthermore, the infiltrating T cell subpopulations mainly consist of oligoclonal expansions, probably specific for persistent antigens. Thus, the characterization of the cells implicated in the aortic valve calcification and the analysis of the antigens to which those cells respond to is of utmost importance to develop new therapies alternative to the replacement of the valve itself. However, calcified aortic valves have been only studied so far by histological and immunohistochemical methods, unable to render an in-depth phenotypical and functional cell profiling. Here we present, for the first time, a simple and efficient cytometry-based protocol that allows the identification and quantification of infiltrating inflammatory leukocytes in aortic valve explants. Our cytometry protocol saves time and facilitates the simultaneous analysis of numerous surface and intracellular cell markers and may well be also applied to the study of other cardiac diseases with an inflammatory component.

Spanish HCMV Seroprevalence in the 21st Century.

Human cytomegalovirus (HCMV) is linked to age-related diseases like cardiovascular disease, neurodegenerative conditions, and cancer. It can also cause congenital defects and severe illness in immunocompromised individuals. Accurate HCMV seroprevalence assessment is essential for public health planning and identifying at-risk individuals. This is the first HCMV seroprevalence study conducted in the general Spanish adult population in 30 years. We studied HCMV seroprevalence and HCMV IgG antibody titres in healthy adult donors (HDs) and HCMV-related disease patients from 2010 to 2013 and 2020 to 2023, categorized by sex and age. We compared our data with 1993 and 1999 studies in Spain. The current HCMV seroprevalence among HDs in Spain is 73.48%. In women of childbearing age, HCMV seroprevalence has increased 1.4-fold in the last decade. HCMV-seropositive individuals comprise 89.83% of CVD patients, 69% of SMI patients, and 70.37% of COVID-19 patients. No differences in HCMV seroprevalence or HCMV IgG antibody titres were observed between patients and HDs. A significant reduction in Spanish HCMV seroprevalence among HDs was observed in 1993. However, women of childbearing age have shown an upturn in the last decade that may denote a health risk in newborns and a change in HCMV seroprevalence trends.

Immune Checkpoint Inhibitors for Vaccine Improvements: Current Status and New Approaches.

In recent years, the use of immune checkpoint inhibitors (ICIs) in combination with approved or experimental vaccines has proven to be a promising approach to improve vaccine immunogenicity and efficacy. This strategy seeks to overcome the immunosuppressive mechanisms associated with the vaccine response, thereby achieving increased immunogenicity and efficacy. Most of the information on the use of ICIs combined with vaccines derives from studies on certain anti-tumor vaccines combined with monoclonal antibodies (mAbs) against either cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death-ligand 1 (PD-L1). However, over the past few years, emerging strategies to use new-generation ICIs as molecular adjuvants are paving the way for future advances in vaccine research. Here, we review the current state and future directions of the use of ICIs in experimental and clinical settings, including mAbs and alternative new approaches using antisense oligonucleotides (ASOs), small non-coding RNAs, aptamers, peptides, and other small molecules for improving vaccine efficacy. The scope of this review mainly includes the use of ICIs in therapeutic antitumor vaccines, although recent research on anti-infective vaccines will also be addressed.

Study of Oligonucleotides Access and Distribution in Human Peripheral Blood Mononuclear Cells.

Therapeutic oligonucleotides have achieved great clinical interest since their approval as drug agents by regulatory agencies but their access and distribution in blood cells are not completely known. We evaluated by flow cytometry the ability of short fluorescent scramble oligonucleotides (ON*) to access human peripheral blood mononuclear cells (PBMC) after incubating with ON* during 1 h and 7 days of culture follow-up 'in vitro'. Blood samples were treated with chemically modified oligonucleotides (phosphorothioate backbone and 2' O-Me ends) to resist nuclease digestion under culture conditions. The ON* internalization was determined after discarding the membrane-associated fluorescence by trypan blue quenching. Whereas the oligonucleotide accessed neutrophils and monocytes rapidly, achieving their maximum in 1 h and 24 h, respectively, lymphocytes required 7 days to achieve the maximum (80% of cells) transfection. The ON*ability to access lymphocyte types (T, B, and NK) and T cell subtypes (CD4+, CD8+, and CD4-CD8-) were similar, with T cells being more accessible. Regulatory CD4+ and CD8+ T cells were classified in low and high Foxp3 expressers, whose expression proved not to alter the ON* internalization during the first hour, achieving 53% of CD4+Foxp3+ and 40% of CD8+Foxp3+ cells. Our results contribute to understanding and improving the management of therapeutic ONs.

A Sporothrix spp. enolase derived multi-epitope vaccine confers protective response in BALB/c mice challenged with Sporothrix brasiliensis.

Sporotrichosis is a cosmopolitan mycosis caused by pathogenic species of Sporothrix genus, that in Brazil is often acquired by zoonotic transmission involved infected cats with S. brasiliensis. Previous studies showed that the Sporothrix spp. recombinant enolase (rSsEno), a multifunctional protein with immunogenic properties, could be a promising target for vaccination against sporotrichosis in cats. Nevertheless, the considerable sequence identity (62%) of SsEno with its feline counterpart is a great concern. Here, we report the identification in silico, chemical synthesis and biological validation of six peptides of SsEno with low sequence identity to its cat orthologue. All synthesized peptides exhibit B-cell epitopes on the molecular surface of SsEno and proved to be highly reactive with the serum of infected mice with S. brasiliensis and sera of cats with sporotrichosis. Interestingly, our study revealed that anti-peptide sera did not react with the recombinant enolase from Felis catus (cats, rFcEno), thus, may not trigger autoimmune response in these felines if used as a vaccine antigen. The immunization with peptide mixture (PeptMix) formulated with Freund adjuvant (FA), induced high levels of antigen-specific IgG, IgG1 and IgG2b antibodies that conferred protection upon passive transference in infected BALB/c mice with S. brasiliensis. We also observed, that the FA+PeptMix formulation induced a Th1/Th2/Th17 cytokine profile ex vivo, associated with protecting effect against the experimental sporotrichosis. Our results suggest that the six SsEno-derived peptides here evaluated, could be used as safe antigens for the development of vaccine strategies against feline sporotrichosis, whether prophylactic or therapeutic.

Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix spp.

Introduction: Regulatory T cells (Tregs) have been shown to limit the protective immune response against pathogenic species of the fungus Sporothrix spp, the causal agent of sporotrichosis. However, the specific function of Tregs during vaccination against these fungi is known. Methods: We evaluated the effect of Tregs depletion on the immunogenicity of an experimental recombinant anti-Sporothrix vaccine, using the DEREG mice. In this model, only Foxp3(+) Tregs express eGFP and diphtheria toxin (DT) receptors, and transient Tregs depletion is achieved by DT administration. Results: Tregs depletion enhanced the frequency of specific IFNγ+ T cells (Th1 lymphocytes) and cytokine production after either the first or second vaccine dose. However, depletion of Tregs during the second dose caused greater stimulation of specific Th1 lymphocytes than depletion during the first dose. Similarly, the highest production of IgG, IgG1, and IgG2a anti rSsEno antibody was detected after Tregs depletion during boost immunization compared to the other immunized groups. Importantly, vaccine immunogenicity improvement after Tregs depletion also had an impact on the more efficient reduction of fungal load in the skin and liver after the challenge with S. brasiliensis in an experimental infection model. Interestingly, the reduction in fungal load was greatest in the Tregs depleted group during boosting. Discussion: Our results illustrate that Tregs restrict vaccine-induced immune response and their transient depletion could enhance anti-Sporothrix vaccine immunogenicity. Further studies are required to elucidate whether Tregs depletion may be a way to improve the efficacy of vaccination against Sporothrix spp.

Enzymatic synthesis of capric acid-rich structured lipids and their effects on mice with high-fat diet-induced obesity.

The objective of this study was to produce structured lipids (SLs) by enzymatic acidolysis using Rhizopus oryzae lipase covalently immobilized in a low-cost material. Grape seed oil was used to synthesize SLs containing the medium-chain fatty acid (C10:0) capric acid. SL synthesis led to 38.8% medium-chain fatty acid incorporation with 5 reuses of the enzymatic derivative. The reaction conditions for the synthesis of MLM-TAGs (triacylglycerols with one long- and two medium-chain acyl residues) were at a molar ratio of fatty acid:oil of 3:1, performed at 40 °C and lipase immobilized load of 5% (w/w). The in vivo effects of SLs were studied in Swiss mice fed premade diets: control (C) diet, high-fat diet (HFD) with 100% lipid content as lard, HFD with 50% lipid content as grape seed oil (HG) or HFD with 50% lipid content as capric acid-containing SLs produced from grape seed oil (HG-MCT). Mice from HG and HG-MCT groups had decreases in body weight gain and reductions in the weights of white adipose tissues. In addition, HG and HG-MCT mice had low plasma levels of glucose and total cholesterol, and improvements in the glucose tolerance. HG and HG-MCT diets have remarkable antioxidant properties, since low plasma levels of TBARS (thiobarbituric acid reactive substances, biomarkers of lipid peroxidation) were found in mice fed these diets. Interestingly, TBARS levels in HG-MCT mice were further decreased than values of HG mice. Mice fed HG and HG-MCT diets also showed preservation in the activity of the antioxidant enzyme paraoxonase 1. Both HG and HG-MCT diets promoted reduction of IL-6 and IL-10 production by splenocytes. The capric acid-containing SLs produced from grape seed oil emerges as a functional oil capable to mitigate obesity complications resulting from oxidative stress and inflammation.

Regulatory T cells and vaccine effectiveness in older adults. Challenges and prospects.

Since the discovery of lymphocytes with immunosuppressive activity, increasing interest has arisen in their possible influence on the immune response induced by vaccines. Regulatory T cells (Tregs) are essential for maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammatory diseases. However, they also limit beneficial immune responses by suppressing anti-infectious and anti-tumor immunity. Mounting evidence suggests that Tregs are involved, at least in part, in the low effectiveness of immunization against various diseases where it has been difficult to obtain protective vaccines. Interestingly, increased activity of Tregs is associated with aging, suggesting a key role for these cells in the lower vaccine effectiveness observed in older people. In this review, we analyze the impact of Tregs on vaccination, with a focus on older adults. Finally, we address an overview of current strategies for Tregs modulation with potential application to improve the effectiveness of future vaccines targeting older populations.

Foxp3 Silencing with Antisense Oligonucleotide Improves Immunogenicity of an Adjuvanted Recombinant Vaccine against Sporothrix schenckii.

BACKGROUND: In recent years, there has been great interest in developing molecular adjuvants based on antisense oligonucleotides (ASOs) targeting immunosuppressor pathways with inhibitory effects on regulatory T cells (Tregs) to improve immunogenicity and vaccine efficacy. We aim to evaluate the immunostimulating effect of 2'OMe phosphorothioated Foxp3-targeted ASO in an antifungal adjuvanted recombinant vaccine. METHODS: The uptake kinetics of Foxp3 ASO, its cytotoxicity and its ability to deplete Tregs were evaluated in murine splenocytes in vitro. Groups of mice were vaccinated with recombinant enolase (Eno) of Sporothix schenckii in Montanide Gel 01 adjuvant alone or in combination with either 1 µg or 8 µg of Foxp3 ASO. The titers of antigen-specific antibody in serum samples from vaccinated mice (male C57BL/6) were determined by ELISA (enzyme-linked immunosorbent assay). Cultured splenocytes from each group were activated in vitro with Eno and the levels of IFN-γ and IL-12 were also measured by ELISA. The results showed that the anti-Eno antibody titer was significantly higher upon addition of 8 µM Foxp3 ASO in the vaccine formulation compared to the standard vaccine without ASO. In vitro and in vivo experiments suggest that Foxp3 ASO enhances specific immune responses by means of Treg depletion during vaccination. CONCLUSION: Foxp3 ASO significantly enhances immune responses against co-delivered adjuvanted recombinant Eno vaccine and it has the potential to improve vaccine immunogenicity.

Transient Foxp3(+) regulatory T-cell depletion enhances protective Th1/Th17 immune response in murine sporotrichosis caused by Sporothrix schenckii.

The role of regulatory T cells (Tregs) on protective immunity in fungal infections, is controversial. Sporotrichosis is an emerging and worldwide-distributed subcutaneous mycosis caused by various related thermodimorphic fungi of the genus Sporothrix. Previously, we showed an elevated percent of Tregs around 21 days post-infection (dpi) in C57BL/6 mice infected with either Sporothrix schenckii or Sporothrix brasiliensis, but the effect of these cells in the ongoing infection was not evaluated. Here, we aim to characterize the role of Foxp3+ Tregs in a subcutaneous S. schenckii infection model. The flow cytometric analyses showed that S. schenckii infection elicited an expansion of a splenic CD4+Foxp3+ population, including a subset of Helioslow+ after ex vivo stimulation with S. schenckii-heat killed yeast. Depletion of Tregs in DEREG mice revealed a reduction of fungal burden in the skin and systemically in liver and kidneys, associated with enhanced Th1 and Th17 responses. Altogether, our results reveal for the first time that Tregs depletion in ongoing S. schenckii infection improves the protective antifungal immunity and these data suggest that Tregs modulation could be explored as a potential therapeutic strategy in sporotrichosis.

Progress in the Use of Antisense Oligonucleotides for Vaccine Improvement.

: Antisense oligonucleotides (ASOs) are synthetically prepared short single-stranded deoxynucleotide sequences that have been validated as therapeutic agents and as a valuable tool in molecular driving biology. ASOs can block the expression of specific target genes via complementary hybridization to mRNA. Due to their high specificity and well-known mechanism of action, there has been a growing interest in using them for improving vaccine efficacy. Several studies have shown that ASOs can improve the efficacy of vaccines either by inducing antigen modification such as enhanced expression of immunogenic molecules or by targeting certain components of the host immune system to achieve the desired immune response. However, despite their extended use, some problems such as insufficient stability and low cellular delivery have not been sufficiently resolved to achieve effective and safe ASO-based vaccines. In this review, we analyze the molecular bases and the research that has been conducted to demonstrate the potential use of ASOs in vaccines.

Trigonelline and curcumin alone, but not in combination, counteract oxidative stress and inflammation and increase glycation product detoxification in the liver and kidney of mice with high-fat diet-induced obesity.

The development of obesity-associated complications is related to various pathogenic events including chronic inflammation, oxidative stress and generation of advanced glycation end products (AGEs). Due to their antioxidant, anti-inflammatory and antiglycation properties, trigonelline and curcumin are interesting candidates to counteract complications of obesity and diabetes mellitus. The current study aimed to investigate the effects of treatment with curcumin or trigonelline mixed into yoghurt, alone or in combination, on mice fed high-fat diet (HFD); the focus was mainly on the potential of these phytochemicals to counteract oxidative and glycative stress. Yoghurt alone improved glucose tolerance and reduced proinflammatory cytokine levels in HFD mice; however, it did not affect the antioxidant status. Trigonelline-enriched yoghurt prevented fat accumulation in adipose tissue, improved both insulin sensitivity and glucose tolerance and exerted anti-inflammatory and antiglycation activities (reduced AGEs and AGE receptor levels and increased the levels of components related to AGE detoxification) in liver and kidney of HFD mice. Curcumin-enriched yoghurt exerted anti-inflammatory and potent antioxidant properties (increased antioxidant enzyme activities and decreased lipid peroxidation) in liver and kidney of HFD mice. However, several beneficial effects were nullified when trigonelline and curcumin were administered in combination. Trigonelline and curcumin have emerged as promising complementary therapy candidates for liver and kidney complications associated with obesity. However, the administration of these phytochemicals in combination, at least in HFD mice, was not effective; inhibition of biotransformation processes and/or the reaching of toxic doses during combined treatment may be prevailing over the individual pharmacodynamic actions of these phytochemicals.

Immunization with recombinant enolase of Sporothrix spp. (rSsEno) confers effective protection against sporotrichosis in mice.

In recent years, research has focused on the immunoreactive components of the Sporothrix schenckii cell wall that can be relevant targets for preventive and therapeutic vaccines against sporotrichosis, an emergent worldwide mycosis. In a previous study, we identified a 47-kDa enolase as an immunodominant antigen in mice vaccinated with an adjuvanted mixture of S. schenckii cell wall proteins. Here, we sought to assess the protective potential of a Sporothrix spp. recombinant enolase (rSsEno) formulated with or without the adjuvant Montanide Pet-GelA (PGA) against the S. brasiliensis infection in mice. Mice that were immunized with rSsEno plus PGA showed increased antibody titters against rSsEno and increased median survival time when challenged with S. brasiliensis as compared with mice that had not been immunized or that were immunized with rSsEno alone. Immunization with rSsEno plus PGA induced a predominantly T-helper 1 cytokine pattern after in vitro stimulation of splenic cells with rSsEno: elevated levels of IFN-γ and IL-2, as well as of other cytokines involved in host defense against sporotrichosis, such as TNF-alpha, IL-6, and IL-4. Furthermore, we show for the first time the presence of enolase in the cell wall of both S. schenckii and S. brasiliensis. As a whole, our results suggest that enolase could be used as a potential antigenic target for vaccinal purposes against sporotrichosis.

Prophylactic and therapeutic vaccines against sporotrichosis. Feasibility and prospects.

Sporotrichosis is an emergent subcutaneous mycosis of humans and some animals caused by dimorphic fungi of the genus Sporothrix. The disease occurs worldwide but is endemic or hyperendemic in tropical and subtropical areas. The epidemiology of the disease is changing dramatically, and it is now considered an important zoonosis with high morbidity rates, principally in Brazil, and an opportunistic infection in immunocompromised patients. Due to the limited options currently available to treat invasive fungal infections, including sporotrichosis, and the emergence of drug resistance and toxicity, the development of anti-Sporothrix vaccines has become an area of great interest. This work provides a brief analysis of the feasibility of the development of prophylactic and therapeutic vaccines against sporotrichosis, the main advances achieved to date, future challenges and prospects.

Síndrome de Béguez-Steinbrinck-Higashi: un nuevo epónimo para el síndrome de Chediak-Higashi / Béguez-Steinbrinck-Higashi syndrome: a new eponymous for the Chediak-Higashi syndrome

En diciembre de 1943, el Dr. Antonio María Béguez César detalló en el Boletín de la Sociedad Cubana de Pediatría los aspectos clínicos y hematológicos de una rara afección que padecieron tres niños de una familia santiaguera, quienes fallecieron en sus primeros años de vida. No había informes sobre hallazgos similares en la bibliografía médica, por lo cual se consideró la primera descripción de una enfermedad denominada por él como neutropenia crónica maligna familiar con granulaciones atípicas de los leucocitos, que aún hoy suele divulgarse erróneamente como síndrome de Chediak-Higashi y no como síndrome de Béguez-Steinbrinck-Higashi. Esta enfermedad es una inmunodeficiencia primaria causada por mutaciones en el gen regulador de la función lisosomal, capaz de alterar la formación del fagolisosoma en el neutrófilo y determinar la presencia de gránulos secretores gigantes en su interior, asociadas a un predominio de infecciones recurrentes generadas por bacterias piógenas. Aquí se realiza un recuento histórico del descubrimiento de esta entidad y se actualiza su fisiopatología(AU)

On December 1943, Dr. Antonio María Béguez César detailed in the Journal of the Cuban Pediatric Society the clinical and hematologic aspects of a rare disorder suffered by three children from a family in the locality, who expired during the first years of their lives in Santiago de Cuba. At that moment there was no report about similar findings in the medical literature, therefore it is considered the first description of a disease denominated by him as familial malignant chronic neutropenia with atypical granulations of leucocytes, misleadingly revealed as Chediak-Higashi syndrome instead of Béguez-Steinbrinck-Higashi syndrome. This disease consists of a primary immunodeficiency induced by mutations in the regulator gen of the lysosomal function, which is able to alter the formation of phagolysosoma in the neutrophil and determine the presence of giant secretor granules associated with the predominance of recurrent infections provoked by pyogen bacteria. Here, a brief history of it's discovery as well as an updating of it's physiopathology are carried out(AU)

A Recombinant Enolase-Montanide™ PetGel A Vaccine Promotes a Protective Th1 Immune Response against a Highly Virulent Sporothrix schenckii by Toluene Exposure.

The effect of vaccination in fungal strains that suffered changes in their virulence by exposure to environmental contaminants is largely known. Growing reports of resistance to antifungal drugs and the emergence of new highly virulent strains, possibly acquired in the environment, prompt the design of new vaccines able to prevent and combat emerging mycotic diseases. In this study, we evaluated the protective capacity of an enolase-based vaccine and Montanide PetGel A (PGA) as an adjuvant against S. schenckii with increased virulence by exposure to toluene. The adjuvanted vaccine induced a strong specific Th1 response and protective immunity against a challenge with either wildtype or toluene-adapted S. schenckii in Balb/c mice. This study highlights the role of the adjuvant PGA driving the quality of the anti-sporothrix immunity and the key component in the vaccine efficacy.

Sporothrix brasiliensis induces a more severe disease associated with sustained Th17 and regulatory T cells responses than Sporothrix schenckii sensu stricto in mice.

Little is known about the differences in the CD4+ T-cell response induced by Sporothrix schenckii and Sporothrix brasiliensis, the most virulent species that cause sporotrichosis. Here, the helper (Th) and regulatory T cells (Tregs) responses were evaluated comparatively in a murine model of sporotrichosis on days 7, 21 and 35 after subcutaneous infection with either S. schenckii or S. brasiliensis conidia. The fungal load was measured at the site of infection, as well as in the liver and spleen. The Th1/Th17/Tregs responses were analyzed in the spleen, while the level of IL-2, IL-4, IL-6, TNF-alpha, IFN-É£, IL-17A and IL-10 cytokines were measured at the local site of infection on 24 h postinfections and in sera on the indicated days. S. brasiliensis caused a longer-lasting infection in the skin and chronic systemic dissemination associated to more severe granulomatous lesions. Similar Th1/Th1-Th17/Tregs responses were induced by both S. brasiliensis and S. schenckii on 7th and 21st d.p.i but on 35 d.p.i a reduction of Th1 and Th1-Th17 cells, associated to higher values of Th17/Tregs cells was observed only in S. brasiliensis-infected mice. In summary, S. brasiliensis caused a more severe disease associated with sustained Th17/Tregs responses than S. schenckii in mice.

Sporothrix schenckii Cell Wall Proteins-Stimulated BMDCs Are Able to Induce a Th1-Prone Cytokine Profile In Vitro.

Sporotrichosis is a subcutaneous mycosis affecting humans and other animals. The disease can be acquired by accidental inoculation of the fungus through the skin or through the respiratory system. Sporotrichosis can also be transmitted through bites or scratches by infected cats and more rarely by other animals (zoonotic transmission). Conventional antifungal therapy is especially inefficient in immunocompromised patients, who tend to develop the most severe forms of the disease, thus prompting the search for alternative therapies. Given their antigen-presenting properties, dendritic cells (DCs) have been used in both prophylactic and therapeutic vaccination strategies. Hence, this study aims to assess the use of DCs as a prophylactic tool in sporotrichosis by evaluating the immune profile induced by Sporothrix schenckii cell wall proteins (SsCWP)-stimulated, bone-marrow-derived DCs (BMDCs). Mouse BMDCs were stimulated with SsCWP for 24 h and analyzed for the surface expression of costimulatory molecules and TLR-4, as well as for the secretion of proinflammatory cytokines and IL-10. Following that, activated BMDCs were cocultured with splenocytes for 72 h and had the same cytokines measured in the supernatant. SsCWP-stimulated BMDCs showed higher expression of CD80, CD86, and CD40, but not TLR-4, and higher secretion of IL-6, IL-17A, and TNF. On the other hand, higher levels of IFN-γ, IL-10, and IL-2 were found in the supernatants of the coculture as compared with the BMDCs alone; TNF secretion was almost completely abrogated, whereas IL-6 was only partially inhibited and IL-17A was unaffected. Our results thus suggest that SsCWP-stimulated BMDCs are able to induce a Th1-prone cytokine profile which is known to be protective against other fungal diseases. This result could lead to studies which evaluate the development of prophylactic and/or therapeutic DC-based tools against sporotrichosis.