Person:
Cuéllar Del Hoyo, María Del Carmen

First Name

María Del Carmen

Last Name

Cuéllar Del Hoyo

URI

https://hdl.handle.net/20.500.14352/77704

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Microbiología y Parasitología

Area

Parasitología

Identifiers

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Now showing 1 - 10 of 25

Are fish tropomyosins allergens?
(Annals of Allergy, Asthma & Immunology, 2016) Veleiro, Beatriz; Daschner, Alvaro; González Fernández, Juan; Cuéllar Del Hoyo, María Del Carmen
Project number: 168
Ampliación de los contenidos virtuales, desarrollados en anteriores proyectos de innovación, de las asignaturas de Parasitología e Inmunología como herramienta docente en el Máster de Análisis Sanitarios
(2023) García Rodríguez, Juan José; Castaño Fernández, Catalina; Cuéllar Del Hoyo, María Del Carmen; Escario García-Trevijano, José Antonio; Fonseca Berzal, Cristina Rosa; Gómez Barrio, Alicia; González Fernández, Juan; Ibáñez Escribano, Alexandra; Martínez Grueiro, Mercedes; Nogal Ruiz, Juan José; Ponce Gordo, Francisco; Rodero Martínez, Marta; Espinosa de los Montero Buitrago, Teresa; Lacueva Arnedo, Manuel; Hernández García, Francisco Javier; Pumar Martín, Manuela
A partir de la situación vivida a causa de la COVID-19 en la que tuvimos que adaptarnos a la docencia virtual, hemos descubierto el gran potencial que las herramientas disponibles en nuestro entorno nos ofrecen para poder mejorar la interacción con los alumnos y alumnas; los cuales demandan este tipo de herramientas, ya que al ser nativos tecnológicos se sienten más cómodos en su uso y les facilita un aprendizaje más dinámico. Este hecho nos llevó a solicitar dos proyectos de innovación de forma consecutiva (161 y 302) en los que se virtualizó el contenido práctico de las asignaturas de Parasitología e Inmunología de Grado, respectivamente. Dado el éxito de estas iniciativas, en este proyecto nos planteamos ampliar el uso de este tipo de herramientas en las dos asignaturas del Máster de Análisis Sanitarios en los que participan miembros de este proyecto. Al igual que en los casos anteriores, estos desarrollos se pondrán a disposición del alumnado del Máster, a través del Campus Virtual, para completar y facilitar su formación en las asignaturas de Diagnóstico Parasitológico y Micológico y Diagnóstico Inmunológico. Por otro lado, pensamos que estas herramientas podrían suponer una alternativa óptima para una posible futura docencia virtual, siendo también aplicable a los alumnos que por diferentes motivos no puedan asistir a la docencia presencial, evitando de esta forma, que nuestros alumnos y alumnas pierdan la experiencia práctica de los protocolos realizados en las diferentes técnicas de laboratorio. Dado que nos encontramos en la formación de alumnos de posgrado, en un Máster eminentemente profesionalizante, consideramos indispensable que adquieran una sólida base tanto en el diagnóstico de parásitos, como en la correcta realización de técnicas inmunológicas que posteriormente se completarán en su período práctico. Esto nos ha movido a pensar en el desarrollo de una herramienta que facilite la comprensión de los conocimientos prácticos no basada en la mera memorización de los mismos, sino con interfaces interactivas que retroalimenten su conocimiento. La aplicabilidad será inmediata en los próximos cursos académicos, una vez desarrollados los contenidos adicionales necesarios para la formación del Máster.
Expansion of T regulatory lymphocytes by murine bone marrow dendritic cells previously stimulated with Anisakis simplex larval antigens
(Memórias do Instituto Oswaldo Cruz, 2021) Zamora, Vega; Rodero Martínez, Marta; Ibáñez Escribano, Alexandra; Andreu-Ballester, Juan C; Méndez, Susana; Cuéllar Del Hoyo, María Del Carmen
BACKGROUND Anisakis simplex antigens present immunomodulatory properties by the induction of tolerogenic dendritic cells (DCs) in mice. OBJECTIVES To study the capacity of DCs stimulated with A. simplex excretory-secretory (ES) or crude extract (CE) to generate Tregs. To investigate in vitro effects of antigens on the metabolic activity of splenocytes induced by LPS or CpG. METHODS Phenotypic and functional characterization of T cells co-cultured with A. simplex-pulsed DCs was performed by Flow cytometry. Lymphocyte mitochondrial respiratory activity was estimated by the Alamar Blue® Assay. FINDINGS In C57BL/6J, CD4+CD25-Foxp3+ and CD8+CD25-Foxp3+ populations increased by CE-stimulated-DCs. In BALB/c, CE-stimulated-DCs caused the expansion of CD4+CD25+Foxp3+IL-10+ and CD8+CD25+Foxp3+IL-10+. IFN-γ expression raised in BALB/c CD4+CD25+ and CD4+CD25- for CE and ES, respectively. ES-stimulated-DCs increased CD4+CD25+ Foxp3+ and CD8+CD25- Foxp3+ expression in T cells. The association of ES or CE with LPS produced the increase in splenocyte activity in C57BL/6J. The association of CE with CpG decreased the proliferation caused by CpG in C57BL/6J. MAIN CONCLUSIONS A. simplex increase the frequency of Tregs, which in turn produce IL-10 and IFN-γ. The host genetic base is essential in the development of anti-Anisakis immune responses (Th2, Th1, Treg).
Serum IgA contributes to the comprehension of Anisakis simplex associated chronic urticaria
(International Immunopharmacology, 2024) González Fernández, Juan; Ullate, Laura; Fernández-Figares Zuleta, Virginia; Rodero Martínez, Marta; Daschner, Alvaro; Cuéllar Del Hoyo, María Del Carmen
The phenotype of allergic diseases associated with Anisakis determines the pattern of cytokines related to antibody production. However, the role of serum IgA and the immunomodulatory mechanisms exerted by active infection of L3 or passive mucosal contact with A. simplex specific antigens has not been studied before. We measured serum cytokine by flow cytometry (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, IL-17A, TGF-β1) and antibody levels (IgE, IgG4, IgA) by ELISA against total and excretory-secretory (ES) antigens, Ani s 3,and the group of major allergens Ani s 1, Ani s 7, and Ani s 13 in sera from 10 patients with gastro-allergic anisakiasis (GAA), 11 Anisakis sensitization associated chronic urticaria (CU+) as well as 17 non-Anisakis-sensitized patients with chronic urticaria (CU-), compared with the urticaria control group (18 subjects). Specific IgE, IgG4 and IgA were high in the GAA, but IgA levels were significantly higher in the CU+ with respect the CONTROL group. We observed higher levels of the ratio IgA/IgG4 in CU+ than GAA group for Ani s 1, Ani s 7, Ani s 13 and ES. Furthermore, chronic urticaria (CU) patients showed significant lower levels of IL-10, IFN-γ and IL-17A than patients without CU. The anti-Ani s 13 IgA/IgG4 ratio correlated positively with pro-inflammatory cytokines and ratios (TNF-α, IL-17A, Th17/Th2, Type1/Type2 and TNF-α/IL-10) in CONTROL group. In general, Anti-Anisakis IgA/G4 ratio was high in CU patients. In conclusion, this study demonstrates the importance of serum IgA because it is associated with chronic urticaria independently of Anisakis sensitization.
Anti-Anisakis antibodies in colon cancer patients and their relationship with γδ T-cells
(Parasitology Research, 2024) Andreu-Ballester, Juan C.; Cuéllar Del Hoyo, María Del Carmen; Colmena-Zaragoza, Javier; Galindo-Regal, Lorena; Hurtado-Marcos, Carolina; González Fernández, Juan; Balciscueta, Zutoia; García-Ballesteros, Carlos; López-Chuliá, Francisca; Jiménez, Ana I.; Llombart-Cussac, Antonio; Shokoofeh Shamsi
Many pathogens are related to carcinogenesis. Chronic infammation, as a result of persistent infection, leads to DNA damage, higher expression of oncogenes, decreased apoptosis and immunosuppression, which are some of the reasons for cancer induction. Among parasites, Schistosoma, Opistorchis and Clonorchis are recognised as infectious agents which contribute to cancer. A relationship between Anisakis and cancer was hypothesised because cellular responses to Anisakis products could result in infammation and DNA damage. Previous research has shown a decrease in CD8+ γδ T-cells and an increase in αβ and γδ T-cell apoptosis in colon cancer (CC) samples. Ninety-two CC patients and 60 healthy subjects were recruited. γδ and αβ T-cells were analysed, and their apoptosis was evaluated. Anti-Anisakis antibodies were tested in sera from CC patients and controls. Anti-Anisakis IgG, IgM, IgA and IgE antibodies were signifcantly higher in CC patients. A signifcant increase in anti-Anisakis IgA levels was observed in patients with angiolymphatic invasion. The number of all γδ T-cells, as well as CD3+ CD4+ αβ T-cells, was signifcantly lower in CC patients. The apoptosis of all T-cells was signifcantly increased in patients with CC. We observed a signifcantly higher percentage of anti-Anisakis IgE positive patients having a defcit of CD3+ γδ T-cells. Our results suggest a relationship between Anisakis and CC.
Differences in circulating γδ T cells in patients with primary colon cancer and relation with prognostic factors
(PLoS One, 2020) Andreu-Ballester, Juan Carlos; Galindo-Regal, Lorena; Hidalgo-Coloma, Julia; Cuéllar Del Hoyo, María Del Carmen; García-Ballesteros, Carlos; Hurtado, Carolina; Uribe, Natalia; Martín, María del Carmen; Jiménez, Ana Isabel; López-Chuliá, Francisca; Llombart-Cussac, Antonio; Yoshihiko Hirohashi
Downregulation of the T cell system has been proposed as a mechanism to block immunity in colonic cancer (CC). However, little has been studied about circulating αβ and γδ T cells and their immunological status in newly diagnosed patients. The aim of this study was to characterize the αβ and γδ T cell subsets in peripheral blood of patients with CC matched with healthy volunteers. In this prospective case-control study, blood samples were obtained from 96 patients with newly diagnosed treatment-naïve infiltrating colonic adenocarcinoma and 48 healthy volunteers. Pathological report at surgery was obtained from all CC patients. A significant decrease in CD3+ γδ T cells and CD3+CD8+ γδ T cells (p<0.001) were observed in CC patients. Apoptosis was significantly increased in all conventional and both αβ and γδ T cell subsets in patients with CC vs healthy subjects. γδ T cells were decreased in peripheral blood of patients with microscopic infiltration in tissues, history of cancer and synchronous colon cancer (p < 0.05). IFN-γ was significantly reduced in CC patients compared to controls. Cytotoxic effector γδ T cells TEMRA (CD8 and CD56) are the proportionally most abundant T cells in peripheral blood of CC patients. Patients with CC present a deep downregulation in the systemic T-cell immunity. These variations are evident through all tumor stages and suggest that a deficiency in γδ T cell populations could be preventing control of tumor progression. This fact prove the role of immunomodulation on CC carcinogenesis.
Association between anti-Anisakis simplex antibodies and interleukin-7 levels
(International Immunopharmacology, 2022) Cuéllar Del Hoyo, María Del Carmen; Rodero Martínez, Marta; Pérez-Griera, Jaime; Galindo-Regal, Lorena; Lopez-Chulia, Francisca; García-Ballesteros, Carlos; Andreu-Ballester, Juan Carlos
IL-7 is a crucial factor for the development of lymphocytes, and it is absolutely necessary for γδ T cells. Mice deficient in L-7 have a deficit of B and αβ T lymphocytes, and an absence of mature γδ TCR cells. IL-7 is essential for the survival, development and maturation of Schistosoma sp., although its production is associated with protection against intestinal helminths. The presence of anti-Anisakis simplex antibodies, especially IgA, is related to a lower frequency in CD3 + CD56 + αβ + lymphocytes and all subpopulations of γδ T cells. In this work, the relationship of IL-7 with humoral and cellular responses against A. simplex in 100 healthy subjects was studied. We have found significantly higher IL-7 levels in anti-A. simplex IgA-positive subjects (p < 0.001). The positivity of anti-A. simplex IgA was associated with a significant reduction in the frequency of CD3 + αβ+ (p < 0.01), CD3 + CD4 + αβ+, CD3 + CD8 + αβ+, CD3 + CD56 + αβ+, CD3 + γδ+, CD3 + CD4-CD8-γδ+ and CD3 + CD56 + γδ+ (p < 0.05) cells. In the case of NKT cells, this same phenomenon was also associated with IgE positivity. There was a weak inverse correlation (Spearman) of IL-7 levels with the frequencies of CD3 + CD4 + αβ+ (-0.125, p = 0.047), CD3 + CD8 + αβ+ (-0.204, p = 0.032), CD3 + CD56 + αβ+ (-0.247, p = 0.007), CD3 + γδ+ (-0.267, p = 0.007), CD3 + CD4-CD8-γδ+ (-0.266, p = 0.003), and CD3 + CD8 + γδ + (-0.302, p = 0.002) cells. The role of NKT cells in the anti-A. simplex response was confirmed and an association between IL and 7 levels and specific antibodies, especially IgA, was demonstrated. The higher production of IL-7 would represent a compensatory mechanism in response to the reduction in lymphocyte populations associated with the response against this parasite.
Rodent Models for the Study of Soil-Transmitted Helminths: A Proteomics Approach
(Frontiers in Cellular and Infection Microbiology, 2021) Montaño, Karen J.; Cuéllar Del Hoyo, María Del Carmen; Sotillo, Javier; Cinzia Cantacessi
Soil-transmitted helminths (STH) affect hundreds of millions worldwide and are some of the most important neglected tropical diseases in terms of morbidity. Due to the difficulty in studying STH human infections, rodent models have become increasingly used, mainly because of their similarities in life cycle. Ascaris suum and Trichuris muris have been proven appropriate and low maintenance models for the study of ascariasis and trichuriasis. In the case of hookworms, despite most of the murine models do not fully reproduce the life cycle of Necator americanus, their proteomic similarity makes them highly suitable for the development of novel vaccine candidates and for the study of hookworm biological features. Furthermore, these models have been helpful in elucidating some basic aspects of our immune system, and are currently being used by numerous researchers to develop novel molecules with immunomodulatory proteins. Herein we review the similarities in the proteomic composition between Nippostrongylus brasiliensis, Heligmosomoides polygyrus bakeri and Trichuris muris and their respective human counterpart with a focus on the vaccine candidates and immunomodulatory proteins being currently studied.
Possible Allergenic Role of Tropomyosin in Patients with Adverse Reactions after Fish Intake
(Immunological Investigations, 2018) Alguacil-Guillén, Marina; Daschner, Alvaro; González Fernández, Juan; Cuéllar Del Hoyo, María Del Carmen
In a recent case report, patient's anti-fish tropomyosin IgE was associated with gastrointestinal symptoms. We aimed to demonstrate on a wider scale that the panallergen tropomyosin should not be limited to invertebrate species and that clinically relevant reactions could be elicited by vertebrate tropomyosin. On the whole, 19 patients with adverse reactions after fish intake and showing negative skin tests with commercial fish extracts were included. Fish tropomyosin was recognized by 10/19 patients' IgE by immunoblotting. All patients with gastrointestinal complaints after fish intake (6/6) showed an IgE band matching with tropomyosin. Cod, albacore, and swordfish tropomyosins were recognized by most patients although 3/10 patients did not claim adverse reactions to these fish species. Immunoblotting with a battery of antigens from different fish species have a high yield of positivity at a band matching with tropomyosin molecular weight, even if they have not been claimed to be causative agents of symptoms. Tropomyosin is therefore a good candidate to be investigated as a clinically relevant fish allergen in patients who report adverse reactions after fish intake.
Lymphopenia in hospitalized patients and its relationship with severity of illness and mortality
(PLoS One, 2021) Andreu-Ballester, Juan Carlos; Pons-Castillo, Aurelio; González-Sánchez, Antonio; Llombart-Cussac, Antonio; Cano Cebrián, María José; Cuéllar Del Hoyo, María Del Carmen; Zivkovic, Aleksandar R.
Background Lymphopenia is associated with various pathologies such as sepsis, burns, trauma, general anesthesia and major surgeries. All these pathologies are clinically expressed by the socalled Systemic Inflammatory Response Syndrome which does not include lymphopenia into defining criteria. The main objective of this work was to analyze the diagnosis of patients admitted to a hospital related to lymphopenia during hospital stay. In addition, we investigated the relationship of lymphopenia with the four levels of the Severity of Illness (SOI) and the Risk of Mortality (ROM). Method and findings Lymphopenia was defined as Absolute Lymphocyte Count (ALC) <1.0 x109/L. ALC were analyzed every day since admission. The four levels (minor, moderate, major and extreme risk) of both SOI and ROM were assessed. A total of 58,260 hospital admissions were analyzed. More than 41% of the patients had lymphopenia during hospital stay. The mean time to death was shorter among patients with lymphopenia on admission 65.6 days (CI95%, 57.3–73.8) vs 89.9 (CI95%, 82.4–97.4), P<0.001. Also, patients with lymphopenia during hospital stay had a shorter time to the mortality, 67.5 (CI95%, 61.1–73.9) vs 96.9 (CI95%, 92.6–101.2), P<0.001. Conclusions Lymphopenia had a high prevalence in hospitalized patients with greater relevance in infectious pathologies. Lymphopenia was related and clearly predicts SOI and ROM at the time of admission, and should be considered as clinical diagnostic criteria to define SIRS.