Immunopathogenesis of tuberculosis: cellular mechanisms and immune modulation Irene Agulló-Ros, Inmaculada Moreno-Iruela, Mercedes Domínguez, José Carlos Gómez-Villamandos, María A. Risalde Veterinary Research, 2025 Tuberculosis (TB) is a worldwide zoonotic disease caused by bacteria members of the Mycobacterium tuberculosis complex (MTC), which affects a wide range of domestic and wildlife species, as well as humans. TB is characterized as a chronic pulmonary infection, primarily affecting the lungs and local lymph nodes (LNs), causing significant respiratory and immunosuppression problems. MTC members have the capability to survive in the host by evading the immune system’s killing mechanisms and persisting within macrophages. This chronic antigenic stimulation promotes the formation of a complex, organized tissue structure known as a tuberculous granuloma, which is a defining cellular response to mycobacteria infections, and is composed of a compact aggregate of immune cells, whose functions are modulated by cytokines. The immune response against TB is complex and nowadays is not completely understood; therefore, the study of its immunopathogenesis becomes essential for evaluating immune-mediated response against mycobacterial infections, and consequently, develop strategies to control and eradicate the propagation of this disease in animals and humans. The aim of this work was to review the literature on key cell populations and immunological markers involved in the formation and development of granulomas in the lungs of humans and animals, and to discuss their potential use in evaluating the efficacy of novel vaccine candidates ‒ a tool that could contribute to TB control.
The orca (Orcinus orca) pituitary gland: an anatomical, immunohistochemical and ultrastructural analysis Paula Alonso-Almorox, Alfonso Blanco, Carla Fiorito, Jose C. Gómez-Villamandos, M. A. Risalde, et al. Frontiers in Neuroanatomy, 2025 The pituitary gland is central to endocrine regulation in vertebrates, coordinating key physiological processes such as growth, reproduction, and stress responses. In cetaceans, and particularly in large odontocetes like orcas (Orcinus orca), understanding pituitary structure is essential for advancing neuroendocrine research and informing welfare and health assessments. Despite their ecological, cognitive, and conservation significance, detailed morphological studies of the orca pituitary gland remain scarce. In this study, we conducted a comprehensive structural and ultrastructural analysis of the orca pituitary gland using postmortem samples from four captive individuals. We combined computed tomography, histology, immunohistochemistry, and transmission electron microscopy to examine the gland’s anatomical organization and cellular composition. Our results reveal features consistent with other cetaceans as well as species-specific characteristics, including the distribution and morphology of endocrine cells within the adenohypophysis and neurohypophysis. These findings provide the first integrated anatomical and ultrastructural reference for the orca pituitary gland, offering valuable insights into cetacean neuroendocrinology and supporting improved species-specific welfare evaluation, health monitoring, and management practices for orcas under human care.
Seroreversion of IgG anti-HEV in HIV cirrhotic patients: A long-term multi-sampling longitudinal study Pedro López‐López, Mario Frias, Angela Camacho, Isabel Machuca, Javier Caballero‐Gómez, et al. Transboundary and Emerging Diseases, 2022 The aim of our study was to evaluate HEV antibody kinetics in HIV/HCV-coinfected patients with cirrhosis. A longitudinal retrospective study was designed. Patients were followed up every 6 months, anti-HEV IgG and IgM antibodies levels and HEV-RNA by qPCR were analyzed. The prevalence and incidence of every HEV infection marker were calculated. The kinetics of anti-HEV IgG and IgM during the follow-up were evaluated. Seventy-five patients comprised the study population. The seroprevalence observed was 17.3%. None showed IgM antibodies or HEV-RNA at baseline. None showed detectable HEV viral load during the study period. After a median follow-up of 5.1 years, 2 of 62 seronegative patients (3.2%) seroconverted to IgG antibody. The incidence for IgM was 2.7%. Of the 13 patients with IgG seropositivity at baseline, 5 (38.5%) seroreverted. Meanwhile, of the 2 patients who exhibited IgM positivity during the study, 1 (50%) showed intermittent positivity. We found that HEV seropositivity is common in HIV/HCV-coinfected cirrhotic patients. A remarkable rate of IgG seroreversions and IgM intermittence was found, limiting the use of antibodies for the diagnosis of HEV infection in this population. This article is protected by copyright. All rights reserved.
Diarrhoea-causing enteric protist species in intensively and extensively raised pigs (Sus scrofa domesticus) in Southern Spain. Part II: Association with Hepatitis E virus susceptibility Antonio Rivero‐Juárez, Alejandro Dashti, Mónica Santín, Pamela C. Köster, Pedro López‐López, et al. Transboundary and Emerging Diseases, 2022 Enteropathogenic parasites can infect a wide range of mammals, including humans, supposing an important zoonotic risk. Hepatitis E virus (HEV) is an emerging foodborne pathogen of increasing public health relevance, affecting both human and animal populations. Because both microorganisms share faecal-oral transmission route they may constitute an excellent model to evaluate the interplay between them. Thus, we aim to evaluate the viral-parasite interactions at the enteric interface in swine. We included pigs of two different breeds farming in South Spain under different production systems. We compared the HEV prevalence by the presence of Giardia duodenalis, Cryptosporidium spp., Balantioides coli, Blastocystis sp., and Enterocytozoon bieneusi in faecal samples. The HEV prevalence was 13.1 (62 out 475, 95% CI: 10.2-16.4). Those pigs infected with Cryptosporidium spp. showed a higher prevalence of HEV (30.8% vs. 12%; p = 0.012). In the same way, animals bearing E. bieneusi seem to have a higher rate of HEV infection (24.2% vs. 12.2%; p = 0.06). According to their location in the gut, animals bearing intracellular enteroparasites showed a higher HEV prevalence than those uninfected (29.6% vs. 12.7%; p = 0.038), meanwhile those carrying extracellular enteroparasites had a lower likelihood to be infected by HEV than those uninfected (12.1% vs. 23.1%; p = 0.071). Those animals bearing both type of enteroparasites showed a similar prevalence of HEV infection than those exhibiting negative for both (20.8% vs. 26.1%; p = 0.763). Our study provides evidence that intracellular and extracellular enteroparasites modulate the susceptibility to HEV infection in pigs. Meanwhile, the presence of extracellular enteroparasites shows a protective effect on the risk of HEV acquisition in swine, whereas intracellular enteroparasites seems to have the opposite effect, favouring the HEV infection. This article is protected by copyright. All rights reserved.
Diarrhoea-causing enteric protist species in intensively and extensively raised pigs (Sus scrofa domesticus) in Southern Spain. Part I: Prevalence and genetic diversity Alejandro Dashti, Antonio Rivero‐Juárez, Mónica Santín, Nadja S. George, Pamela C. Köster, et al. Transboundary and Emerging Diseases, 2022 Numerous protist species are shared between humans and pigs. Among those, Giardia duodenalis, Cryptosporidium spp., and Balantioides coli have a clear public and animal health significance. For other such as Enterocytozoon bieneusi and Blastocystis sp., their impact in animal health has not been fully stablished. Little information is currently available on the molecular diversity of these protists in swine populations. To fill this gap, we molecularly assessed G. duodenalis, Cryptosporidium spp., B. coli, Blastocystis sp., and E. bieneusi in faecal samples from Iberian and Large White pigs raised under different (intensive and/or extensive) management systems in southern Spain. A total of 151 extensively raised Iberian pigs, 140 intensively raised Iberian pigs, and 184 intensively raised Large White pigs were investigated. Blastocystis sp. was the agent most prevalently found (47.8%), followed by B. coli (45.5%), G. duodenalis (10.7%), E. bieneusi (6.9%), and Cryptosporidium spp. (5.5%). Blastocystis sp. was significantly less prevalent in intensively raised Iberian pigs (22.9%) than in their extensively raised counterparts (51.0%) or in intensively raised Large White pigs (64.1%). A significant higher prevalence was found for G. duodenalis), Cryptosporidium spp., and E. bieneusi in Large White pigs than Iberian pigs. Balantioides coli was similarly distributed (40.0-51.1%) in all three investigated swine populations. Sequence analyses revealed the presence of G. duodenalis assemblage E, two Cryptosporidium species (Cryptosporidium scrofarum and Cryptosporidium suis), B. coli (genotypes A and B), Blastocystis sp. (ST1, ST3, and ST5), E. bieneusi (EbpA, EbpC, EbpD, O, and a novel genotype named PigSpEb2). Novel genotype PigSpEb2 was found alone or in combination with EbpA. Data suggest a widespread exposure to protist enteroparasites in domestic pig populations irrespectively of breed and raising management system. Many of the species/genotype identified have zoonotic potential and might represent a public health concern. This article is protected by copyright. All rights reserved.
Immunohistochemical expression of aromatase cyp19a1a and cyp19a1b in the ovary and brain of zebrafish (Danio rerio) exposed to different concentrations of bisphenol A Maria A Risalde, Ana Mª Molina, Antonio J Lora, Nahum Ayala, Jose C Gómez-Villamandos, et al. Aquatic Toxicology, 2021 Bisphenol A (BPA) is used to produce plastic and plastic derived products in multitude of daily utensils, being one of the industrial compounds most widely used. This endocrine disrupting chemical (EDCs) is a well-known environmental pollutant released into the aquatic environment from industrial wastewater, sewage sludge or landfill leachate. Aromatases are considered potential targets of EDCs with characteristics that make them suitable biomarkers of exposure to their effects. The main objective of our study was to evaluate the expression of cyp19a aromatase as a toxicological endpoint after BPA exposure through the identification and assessment of alterations of the main cells responsible for cyp19a1a and cyp19a1b expression in the zebrafish ovary and brain using different concentrations of BPA in water. Immunohistochemistry was used to analyze the expression of these enzymes in female zebrafish exposed and not exposed to different concentrations of BPA (1, 10, 100 and 1000 μg / L) in water (n = 6/group) for 14 days. The results obtained in this study showed that the cyp19a aromatase system, involved in the synthesis of steroid compounds, is specially located in distinct oocyte stages in the ovary (cyp19a1a) and in radial glial cells of the brain (cyp19a1b). An overexpression of these aromatases was observed after BPA exposure in zebrafish, peaking from a concentration of 10 µg/L and showing to be good biomarkers of exposure to identify the early effects of low BPA concentrations. To our knowledge, this study is the first to localize and quantify the expression of cyp19a1a and cyp19a1b in the cells of brain and ovary after fish exposure to different BPA concentrations in water.
Evaluation of a non-invasive screening approach to determine hepatitis e virus status of pig farms Maria A Risalde, Antonio Rivero‐Juarez, Mario Frias, Israel Olivas, Pedro Lopez‐Lopez, et al. Veterinary Record, 2020 Background Identifying pig farms infected with hepatitis E virus (HEV) is a key aspect to implement surveillance programmes for this emerging zoonotic agent. Detection of HEV in blood has several drawbacks, including animal handling, economic costs and animal stress. The objective of this study was to evaluate the effectiveness of a non-invasive screening approach for determining the HEV status of pig farms under different management systems. Methods Forty stool samples randomly collected from the pen floor of 17 intensive pig farms and the yard of nine extensive ones were tested for HEV RNA. The invasive method used to confirm the HEV status of the farm was HEV RNA analysis of serum samples randomly collected from 40 animals on each farm. Results Twenty-one HEV-positive farms were detected by invasive and non-invasive methods. No positive serum or stool samples were detected on five intensive farms. A high intertest agreement (K=1; P<0.00001) was observed between both methodologies, showing the stool screening approach a 100 per cent of sensitivity and specificity with respect to the invasive method. Likewise, a significant negative relationship was observed between the HEV within-farm prevalence and the number of the first HEV-positive stool sample found (Spearman’s rho=−0.64; P=0.0004). This negative relationship was higher in intensively managed farms. Conclusion This non-invasive screening approach could be reliably applied in a large-scale surveillance programme for determining the HEV status of pig farms under different management systems.
BVDV permissiveness and lack of expression of co-stimulatory molecules on PBMCs from calves pre-infected with BVDV María A. Risalde, Fernando Romero-Palomo, Cristina Lecchi, Fabrizio Ceciliani, Chiara Bazzocchi, et al. Comparative Immunology Microbiology and Infectious Diseases, 2020 Bovine viral diarrhea virus (BVDV) has been detected in peripheral blood mononuclear cells (PBMCs) of immunocompetent animals, not being clear whether the development of a specific humoral immune response can prevent BVDV infection. The aim of this study was to evaluate the ability of non-cytopathic BVDV to replicate and produce infectious virus in PBMCs from calves pre-infected with BVDV and to elucidate the immunomodulatory effect of BVDV on these cells in an in vitro model. Quantification of virus was by quantitative PCR, while its replicative capacity and shedding into the extracellular environment was evaluated by viral titration. Apoptosis was assessed by flow cytometry analysis of annexin V and propidium iodide, and by expression of caspase-3/7. Flow cytometry was used to analyze the expression of CD14/CD11b/CD80, CD4/CD8/CD25, MHC-I/MHC-II and B-B2 markers. Our results showed that PBMCs from cattle naturally infected with BVDV were more susceptible to in vitro BVDV infection and showed a more severe apoptosis response than those from naïve animals. Non-cytopathic BVDV in vitro infection also resulted in a lack of effect in the expression of antigen presentation surface markers. All these findings could be related to the immunosuppressive capacity of BVDV and the susceptibility of cattle to this infection.
IMMUNOMODULATION MECHANISMS DEVELOPED BY BOVINE VIRAL DIARRHEA VIRUS AND ITS ROLE IN THE ESTABLISHMENT OF THE BOVINE RESPIRATORY DISEASE COMPLEX Encyclopedia of Virology New Research Volume 6 6 Volume Set, 2020
Hepatitis E virus infection in equines in Spain Ignacio García‐Bocanegra, Antonio Rivero, Javier Caballero‐Gómez, Pedro López‐López, David Cano‐Terriza, et al. Transboundary and Emerging Diseases, 2019
