Evaluation of an O2-Substituted (1–3)-β-D-Glucan, Produced by Pediococcus parvulus 2.6, in ex vivo Models of Crohn’s Disease

Efecte antiinflamatori de la malaltia de Crohn; Immunomodulació; Exopolisacàrids bacteriansEfecto antiinflamatorio de la enfermedad de Crohn; Inmunomodulacion; Exopolisacáridos bacterianosCrohn's disease anti-inflammatory effect; Immunomodulation; Bacterial exopolysaccharides1,3-β-glucans are extracellular polysaccharides synthesized by microorganisms and plants, with therapeutic potential. Among them, the O2-substituted-(1–3)-β-D-glucan, synthesized by some lactic acid bacteria (LAB), has a prebiotic effect on probiotic strains, an immunomodulatory effect on monocyte-derived macrophages, and potentiates the ability of the producer strain to adhere to Caco-2 cells differentiated to enterocytes. In this work, the O2-substituted-(1–3)-β-D-glucan polymers produced by GTF glycoyltransferase in the natural host Pediococcus parvulus 2.6 and in the recombinant strain Lactococcus lactis NZ9000[pNGTF] were tested. Their immunomodulatory activity was investigated in an ex vivo model using human biopsies from patients affected by Crohn’s disease (CD). Both polymers had an anti-inflammatory effect including, a reduction of Interleukine 8 both at the level of its gene expression and its secreted levels. The overall data indicate that the O2-substituted-(1–3)-β-D-glucan have a potential role in ameliorating inflammation via the gut immune system cell modulation.This work was supported by the Spanish Ministry of Science, Innovation, and Universities (grant RTI2018-097114-B-I00), by the Fondo de Investigación Sanitaria, grant number PI12/00263, and by CIBERehd

Mobilized memories: deployments of the past in the present and the future

Coordinators: Francisco Ferrándiz Martín, (ILLA, CSIC), Reyes Mate Rupérez (IFS, CSIC).Memory processes —as selective displays of the past in the present— are an essential component of the configuration and development of all human societies and affect areas that range from everyday gestures to high-level politics. The unfolding of memory is especially important in the constitution of individual and collective identities, and its enormous potential for cohesion is only comparable to its great capacity to generate exclusion, difference, and dispute. It is impossible to understand historical or contemporary conflicts in depth without analyzing the memory processes in which they are or have been immersed. Hence the strategic importance of this challenge for an institution such as CSIC. The approach to memory and memory processes is necessarily interdisciplinary, as it can be analyzed through the scientific fields of neurobiology, philosophy, sociology, political science, psychology, literary studies, religious studies, cultural studies, historiography, social anthropology, archeology, or cultural geography, among others. By reviewing the main historical, theoretical and thematic anchors of memory studies –with a special emphasis on CSIC-based research–, as well as their prospects for the future, this challenge proposes to proactively foster this interdisciplinarity to build a common analytical language substantially richer and more sophisticated than each of its individual parts

Case Report : X-Linked SASH3 Deficiency Presenting as a Common Variable Immunodeficiency

SASH3 is a lymphoid-specific adaptor protein. In a recent study, SASH3 deficiency was described as a novel X-linked combined immunodeficiency with immune dysregulation, associated with impaired TCR signaling and thymocyte survival in humans. The small number of patients reported to date showed recurrent sinopulmonary, cutaneous and mucosal infections, and autoimmune cytopenia. Here we describe an adult patient previously diagnosed with common variable immunodeficiency (CVID) due to low IgG and IgM levels and recurrent upper tract infections. Two separate, severe viral infections drew our attention and pointed to an underlying T cell defect: severe varicella zoster virus (VZV) infection at the age of 4 years and bilateral pneumonia due type A influenza infection at the age of 38. Genetic testing using an NGS-based custom-targeted gene panel revealed a novel hemizygous loss-of-function variant in the SASH3 gene (c.505C>T/p.Gln169*). The patient's immunological phenotype included marked B cell lymphopenia with reduced pre-switch and switch memory B cells, decreased CD4 + and CD8 + naïve T cells, elevated CD4 + and CD8 + T cells, and abnormal T cell activation and proliferation. The patient showed a suboptimal response to Streptococcus pneumoniae (polysaccharide) vaccine, and a normal response to Haemophilus influenzae type B (conjugate) vaccine and SARS-CoV-2 (RNA) vaccine. In summary, our patient has a combined immunodeficiency, although he presented with a phenotype resembling CVID. Two severe episodes of viral infection alerted us to a possible T-cell defect, and genetic testing led to SASH3 deficiency. Our patient displays a milder phenotype than has been reported previously in these patients, thus expanding the clinical spectrum of this recently identified inborn error of immunity

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