Authors: Martire Greco, Daiana; Landoni, Verónica Inés; Chiarella, Paula; Rodriguez Rodrigues, Nahuel Emiliano; Schierloh, Luis Pablo; Rearte, María Bárbara; Isturiz, Martín Amadeo; Fernández, Gabriela Cristina
Publication Date: 2014.
Language: English.
Abstract:
Secondary infections due to post-sepsis immunosuppression is a major cause of death in septic patients. Strategies aimed at restoring immune functions offer a new perspective. We used LPS-immunosuppressed (IS) mice to analyze the effects of all-trans Retinoic Acid (ATRA) on different immune parameters. IS mice showed decreased lymphocyte and increased myeloid-derived suppressor cells (MDSC) counts in lymph nodes. They also showed an impaired in vitro T cell proliferation,mediated by MDSC. ATRA administration restored T cell proliferation, associated to a decreased number of live MDSC. IS mice treated with ATRA showed an increased number of CD4+ and CD8+ T cells. ATRA partially improved the primary humoral immune response, even when the immunossuppression was first established, and ATRA administered afterwards. Our results demonstrate that ATRA restores immunocompetence, modulating the number of leukocytes and the survival of MDSC,representing a supplementary potential strategy in the treatment of the immunosuppressive state of sepsis.
Author affiliation: Martire Greco, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Landoni, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Chiarella, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Rodriguez Rodrigues, Nahuel Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Schierloh, Luis Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Fernández, Gabriela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Rearte, Barbara; Maglioco, Andrea Florencia; Machuca, Damián Gabriel; Martire Greco, Daiana; Landoni, Verónica Inés; Rodriguez Rodrigues, Nahuel Emiliano; Meissl, Roberto Jose; Fernández, Gabriela Cristina; Isturiz, Martín Amadeo
Publication Date: 2013.
Language: English.
Abstract:
Prior exposure to endotoxins renders the host temporarily refractory to subsequent endotoxin challenge (endotoxin tolerance). Clinically, this state has also been pointed out as the initial cause of the non-specific humoral and cellular immunosuppression described in these patients. We recently demonstrated the restoration of immune response with mifepristone (RU486), a receptor antagonist of glucocorticoids. Here we report the treatment with other modulators of glucocorticoids, i.e. dehydroepiandrosterone (DHEA), a hormone with anti-glucocorticoid properties, or metyrapone (MET) an inhibitor of corticosterone synthesis. These drugs were able to partially, but significantly, restore the humoral immune response in immunosuppressed mice. A significant recovery of proliferative responsiveness was also observed when splenocytes were obtained from DHEA- or MET-treated immunosuppressed mice. In addition, these treatments restored the hypersensitivity response in immunosuppressed mice. Finally, although neither DHEA nor MET improved the reduced CD4 lymphocyte count in spleen from immunosuppressed mice, both treatments promoted spleen architecture reorganization, partially restoring the distinct cellular components and their localization in the spleen. The results from this study indicate that DHEA and MET could play an important role in the restoration of both adaptive humoral and cellular immune response in LPS-immunosuppressed mice, reinforcing the concept of a central involvement of endogenous glucocorticoids on this phenomenon.
Author affiliation: Rearte, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Maglioco, Andrea Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Machuca, Damián Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Martire Greco, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Landoni, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Rodriguez Rodrigues, Nahuel Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Meissl, Roberto Jose. Academia Nacional de Medicina de Buenos Aires; Argentina
Author affiliation: Fernández, Gabriela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Author affiliation: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Zambernardi König, María Agustina; Chiodetti, Ana Laura; Meier, Dominik; Cabanne, Ana; Nachman, Fabio; Solar, Héctor; Rumbo, Carolina; Gondolesi, Gabriel Eduardo; Rumbo, Martín
Publication Date: 2014.
Language: English.
Abstract:
Background and Aims Acute cellular rejection (ACR) and infections are leading causes of graft loss and death in intestinal transplant patients. Our aim was to evaluate the impact of maintenance immunosuppressive therapies on the expression of pro-inflammatory mediators in small bowel at ACR diagnosis. Materials and Methods We analyzed expression levels of Th1-associated genes, IFNG, CXCL10, and CXCL11 by qPCR in 46 selected graft biopsies unequivocally assigned to mild ACR (n = 14) or normal histopathology and clinical condition (n = 32) from 15 patients receiving two different immunosuppressive (IS) schemes. Double treatment: corticosteroids and tacrolimus (n = 17) and triple treatment: sirolimus or mycophenolate mofetil in addition to the basal therapy (n = 29). Results IFNG, CXCL10, and CXCL11 were induced during rejection (p < 0.05; p < 0.005, and p < 0.05, respectively). However, when rejection and control groups were classified according to immunosuppressive treatment, in the rejection group, significant differences of IFNG, CXCL10, and CXCL11 expression (p < 0.001; p < 0.005, and 0.01, respectively) were detected, whereas no differences were observed in the control group. Conclusion Gene expression of Th1 response mediators is higher during ACR. Triple IS group showed significantly lower expression of pro-inflammatory Th1 mediators during mild ACR indicating that use of these markers to monitor rejection can be affected by the IS treatment used.
Author affiliation: Zambernardi König, María Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Fundación Favaloro; Argentina
Author affiliation: Chiodetti, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina
Author affiliation: Meier, Dominik. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Favaloro; Argentina
Author affiliation: Cabanne, Ana. Fundación Favaloro; Argentina
Author affiliation: Nachman, Fabio. Fundación Favaloro; Argentina
Author affiliation: Solar, Héctor. Fundación Favaloro; Argentina
Author affiliation: Rumbo, Carolina. Fundación Favaloro; Argentina
Author affiliation: Gondolesi, Gabriel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Favaloro; Argentina
Author affiliation: Rumbo, Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Salva, Maria Susana; Marranzino, Gabriela; Villena, Julio Cesar; Agüero, Graciela; Alvarez, Gladis Susana
Publication Date: 2014.
Language: English.
Abstract:
This work evaluated the capacity of two probiotic strains, Lactobacillus casei CRL431 and Lactobacillus rhamnosus CRL1506, to protect against myelosuppression and immunosuppression in cyclophosphamide (Cy)-treated mice. Changes inmature granulocytes and progenitor cells in bonemarrow (BM) and blood were studied. In addition, the ability of probiotics to accelerate the recovery of the immune response against the opportunistic pathogen Candida albicans was evaluated.We demonstrated for the first time that the preventive treatmentwith immunomodulatory lactobacilli such as L. casei CRL431 or L. rhamnosus CRL1506 was able to increase immature myeloid progenitors in the BM, allowing an early recovery of myeloid cells after Cy administration. Probiotic lactobacilli were also capable to induce an early recovery of neutrophils in blood, improve phagocytic cells recruitment to infectious sites and increase the resistance against the opportunistic pathogen C. albicans. Although deeper studies regarding the cellular and molecularmechanisms of probiotic actions are needed, these findings support the idea that strains like CRL431 and CRL1506 may accelerate the recovery of Cy-caused immunosuppression by immunopotentiating myeloid cells. Then, probiotic lactobacilli have the potential to be used as alternatives for lessening chemotherapy-induced immunosuppression in cancer patients.
Author affiliation: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina
Author affiliation: Marranzino, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina
Author affiliation: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina
Author affiliation: Agüero, Graciela. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Bioquimica Clinica Aplicada. Catedra de Bioquimica Clinica I; Argentina
Author affiliation: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Bioquimica Clinica Aplicada. Catedra de Bioquimica Clinica I; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Blidner, Ada Gabriela; Mendez Huergo, Santiago Patricio; Cagnoni, Alejandro; Rabinovich, Gabriel Adrian
Publication Date: 2015.
Language: English.
Abstract:
Programs that control immune cell homeostasis are orchestrated through the coordinated action of a number of regulatory cell populations, including regulatory T cells, regulatory B cells, myeloid-derived suppressor cells, alternatively-activated macrophages and tolerogenic dendritic cells. These regulatory cell populations can prevent harmful inflammation following completion of protective responses and thwart the development of autoimmune pathology. However, they also have a detrimental role in cancer by favoring escape from immune surveillance. One of the hallmarks of regulatory cells is their remarkable plasticity as they can be positively or negatively modulated by a plethora of cytokines, growth factors and co-stimulatory signals that tailor their differentiation, stability and survival. Here we focus on the emerging roles of galectins, a family of highly conserved glycan-binding proteins in regulating the fate and function of regulatory immune cell populations, both of lymphoid and myeloid origins. Given the broad distribution of circulating and tissue-specific galectins, understanding the relevance of lectin-glycan interactions in shaping regulatory cell compartments will contribute to the design of novel therapeutic strategies aimed at modulating their function in a broad range of immunological disorders.
Author affiliation: Blidner, Ada Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Author affiliation: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Author affiliation: Cagnoni, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Author affiliation: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas
Authors: Malvicini, Mariana; Ingolotti, Mariana; Piccioni, Flavia Valeria; García, Mariana Gabriela; Bayo Fina, Juan Miguel; Atorrasagasti, María Catalina; Alaniz, Laura Daniela; Aquino, Jorge Benjamin; Espinoza, Jaime A.; Gidekel, Manuel; Scharovsky, Olga Graciela; Matar, Pablo; Mazzolini Rizzo, Guillermo Daniel
Publication Date: 2011.
Language: English.
Abstract:
Immunotherapy-based strategies for gastrointestinal carcinomas (GIC) have been exploited so far, but these approaches have to face strong mechanisms of immune escape induced by tumours. We previously demonstrated that sub-therapeutic doses of an adenovirus expressing IL-12 genes (AdIL-12) mediated a potent antitumour effect against subcutaneous (s.c.) colorectal carcinomas (CRC) in mice pre-treated with low doses of cyclophosphamide (Cy). In our study we used this combination to assess its impact on the immunosuppressive microenvironment. In s.c. CRC model we demonstrated that non-responder mice failed to decrease Tregs in tumour, spleen and peripheral blood. Reconstitution of Tregs into tumour-bearing mice treated with combined therapy abolished the antitumoural effect. In addition, Cy + AdIL-12 modified Tregs functionality by inhibiting the in vitro secretion of IL-10 and TGF-β and their ability to inhibit dendritic cells activation. Combined treatment decreased the number of myeloid-derived suppressor cells (MDSCs) in comparison to non-treated mice and, interestingly, administration of Tregs restored splenic MDSCs population. Furthermore, combined therapy potently generated specific cytotoxic IFN-γ-secreting CD4+ T cells able to eradicate established CRC tumours after adoptive transfer. Finally, we evaluated the combination on disseminated CRC and pancreatic carcinoma (PC). Cy + AdIL-12 were able to eradicate liver metastatic CRC (47%) and PC tumour nodules (40%) and to prolong animal survival. The results of this study support the hypothesis that Cy + AdIL-12 might be a valid immunotherapeutic strategy for advanced GIC.
Author affiliation: Malvicini, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
Author affiliation: Ingolotti, Mariana. Universidad Austral; Argentina
Author affiliation: Piccioni, Flavia Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
Author affiliation: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
Author affiliation: Bayo Fina, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
Author affiliation: Atorrasagasti, María Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
Author affiliation: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
Author affiliation: Aquino, Jorge Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
Author affiliation: Espinoza, Jaime A.. Universidad Adolfo Ibañez; Chile. Universidad de La Frontera; Chile
Author affiliation: Gidekel, Manuel. Universidad Adolfo Ibañez; Chile
Author affiliation: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Author affiliation: Matar, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina
Author affiliation: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas