Prolonged dysbiosis and altered immunity under nutritional intervention in a physiological mouse model of severe acute malnutrition.

Severe acute malnutrition (SAM) is a multifactorial disease affecting millions of children worldwide. It is associated with changes in intestinal physiology, microbiota, and mucosal immunity, emphasizing the need for multidisciplinary studies to unravel its full pathogenesis. We established an experimental model in which weanling mice fed a high-deficiency diet mimic key anthropometric and physiological features of SAM in children. This diet alters the intestinal microbiota (less segmented filamentous bacteria, spatial proximity to epithelium), metabolism (decreased butyrate), and immune cell populations (depletion of LysoDC in Peyer's patches and intestinal Th17 cells). A nutritional intervention leads to a fast zoometric and intestinal physiology recovery but to an incomplete restoration of the intestinal microbiota, metabolism, and immune system. Altogether, we provide a preclinical model of SAM and have identified key markers to target with future interventions during the education of the immune system to improve SAM whole defects.

Clinical effects of immunization, bleeding, and albumin-based fluid therapy in horses used as immunoglobulin source to produce a polyspecific antivenom (Echitab-plus-ICP) towards venoms of African snakes.

During the production of snake antivenoms, the animals used as immunoglobulin source are subjected to processes that could deteriorate their physical condition. Therefore, these conditions must be carefully designed and validated. In this work, the immunization and bleeding protocols applied to horses used to produce the African polyspecific antivenom EchiTAb-plus-ICP were evaluated regarding their effects on the horses' health. The study focused on horses that had been previously immunized with venoms and then received periodic booster venom injections for antivenom production. It was found that the periodic immunization with 5 mg of a mixture of venoms of Bitis arietans, Echis ocellatus, Dendroaspis polylepis, and Naja nigricollis did not induce systemic signs of envenomation, and only caused mild swelling at the injection site, which did not evolve to abscesses, fistulas, or fibrosis. Three consecutive days of bleeding, collecting 6-8 L of blood per day, and self-transfusing the red blood cells (RBC) in the second and third days, did not induce evident cardiorespiratory alterations. However, this procedure caused significant reductions in RBC, hematocrit, hemoglobin, and total plasma protein values. Seven weeks after bleeding, these parameters were recovered, and horses were ready for the next immunization/bleeding cycle. The intravenous administration of equine albumin, at a dose of 2 g/kg body weight, increased the apparent plasma volume and the albumin concentration. However, this procedure induced early adverse reactions and transient alterations of the serum levels of the enzyme gamma-glutamyl transferase (GGT), thus suggesting some degree of hepatic injury. It was concluded that immunization and bleeding as described in this work do not cause significant clinical alterations in the horse's health, except for a transient drop in some hematological parameters. The albumin-based fluid therapy used does not hasten the recovery after bleeding but instead induces adverse events in the animals.

Peyer's patch phagocytes acquire specific transcriptional programs that influence their maturation and activation profiles.

Peyer's patches (PPs) are secondary lymphoid organs in contact with the external environment via the intestinal lumen, thus combining antigen sampling and immune response initiation sites. Therefore, they provide a unique opportunity to study the entire process of phagocyte differentiation and activation in vivo. Here, we deciphered the transcriptional and spatial landscape of PP phagocyte populations from their emergence in the tissue to their final maturation state at homeostasis and under stimulation. Activation of monocyte-derived Lysozyme-expressing dendritic cells (LysoDCs) differs from that of macrophages by their upregulation of conventional DC (cDC) signature genes such as Ccr7 and downregulation of typical monocyte-derived cell genes such as Cx3cr1. We identified gene sets that distinguish PP cDCs from the villus ones and from LysoDCs. We also identified key immature, early, intermediate, and late maturation markers of PP phagocytes. Finally, exploiting the ability of the PP interfollicular region to host both villous and subepithelial dome emigrated cDCs, we showed that the type of stimulus, the subset, but also the initial location of cDCs shape their activation profile and thus direct the immune response. Our study highlights the importance of targeting the right phagocyte subset at the right place and time to manipulate the immune response.

From Species to Regional and Local Specialization of Intestinal Macrophages.

Initially intended for nutrient uptake, phagocytosis represents a central mechanism of debris removal and host defense against invading pathogens through the entire animal kingdom. In vertebrates and also many invertebrates, macrophages (MFs) and MF-like cells (e.g., coelomocytes and hemocytes) are professional phagocytic cells that seed tissues to maintain homeostasis through pathogen killing, efferocytosis and tissue shaping, repair, and remodeling. Some MF functions are common to all species and tissues, whereas others are specific to their homing tissue. Indeed, shaped by their microenvironment, MFs become adapted to perform particular functions, highlighting their great plasticity and giving rise to high population diversity. Interestingly, the gut displays several anatomic and functional compartments with large pools of strikingly diversified MF populations. This review focuses on recent advances on intestinal MFs in several species, which have allowed to infer their specificity and functions.

Prevalencia de niveles bajos de 25(OH)-vitamina D en universitarios costarricenses / Prevalence of low 25 OH-Vitamin D levels in Costa Rican university students

Resumen Objetivo: Describir la prevalencia de hipovitaminosis D3 y sus características clínicas y bioquímicas en una población de universitarios costarricenses. Métodos: Investigación transversal y descriptiva en un total de 118 individuos sanos, de ambos sexos, con edades entre los 18-43 años. Se preguntó sobre historia familiar de enfermedades crónicas, nivel de exposición al sol, uso de protectores solares, presión arterial. En el laboratorio, se analizaron en suero: glucosa, calcio, fosfato, hormona paratiroidea, insulina, 25 OH-Vitamina D e inmunoglobulina E. Se calcularon el índice de masa corporal y el modelo matemático de evaluación para la homeostasis de la resistencia a la insulina. Resultados: La prevalencia de hipovitaminosis D3 (<30 ng/mL) en este estudio fue de 25% sin diferencia significativa por sexo. La concentración promedio de 25 OH-vitamina D fue 36,2 ng/mL, con valores que van desde 14,5 a 59,5 ng/mL. Un total de 26 estudiantes presentaba insuficiencia de 25 OH-vitamina D (21-29 ng/mL) y solamente 4 fueron clasificados con una deficiencia grave (<20 ng/mL). No se encontraron casos de hipervitaminosis D3 (>100 ng/mL) en la muestra de estudio. Al comparar aquellos sujetos con deficiencia de 25 OH-Vitamina D3 contra los que presentaron niveles séricos normales de esta vitamina, se observaron diferencias significativas solamente en dos parámetros bioquímicos: insulina (10,9 ± 7,4 µUI/ mL vs 8,3 ± 4,1 µUI/mL; p=0,017) y el índice HOMA IR (2,48 ± 1,86 vs 1,85 ± 0,3; p=0,002). Cerca de la mitad de los estudiantes relataron antecedentes familiares de diabetes mellitus (49,2%) e hipertensión arterial (52,9%). El 29% de los participantes tenía sobrepeso y obesidad. Conclusiones: El 25% de los sujetos estudiados presentó deficiencia de 25 OH-Vitamina D. Estos sujetos, a su vez, presentaron una mayor prevalencia de hiperinsulinemia y resistencia a la insulina en comparación con personas con concentraciones normales de esta vitamina. También existe una alta prevalencia de factores de riesgo entre los familiares de la población joven, los cuales podrían aumentar el riesgo de estos estudiantes de padecer diabetes mellitus o enfermedades cardiovasculares en un futuro cercano.

Abstract Objective: To determine the prevalence of hypovitaminosis D3 in a population of Costa Rican University students and describe its clinical and biochemical characteristics. Methods: Cross-sectional and descriptive research with a total of 118 healthy individuals of both genders aged between 18-43 years. Questions were asked about family history of chronic diseases, level of sun exposure, use of sunscreens, blood pressure. In the laboratory, glucose, calcium, phosphate, parathyroid hormone, insulin, 25 OH-Vitamin D and immunoglobulin E were analyzed in serum. Body Mass Index and the mathematical assessment model for the homeostasis of insulin resistance were calculated. Results: The prevalence of hypovitaminosis D3 (<30 ng/mL) in this study was 25% with no significant difference by sex. The average concentration of 25 OH-Vitamin D was 36.2 ng/mL, with values ranging from 14.5 to 59.5 ng/mL. A total of 26 students had 25 OH- Vitamin D insufficiency (21-29 ng/mL) and only 4 were classified as severely deficient (<20 ng/mL). No cases of hypervitaminosis D3 (> 100 ng/mL) were found in the study sample. When comparing those subjects with 25 OH-Vitamin D3 deficiency against those with normal serum levels of this vitamin, significant differences were observed only in two biochemical parameters: insulin (10.9 ± 7.4 µIU/mL vs 8.3 ± 4.1 µUI/mL; p=0.017) and the HOMA IR index (2.48 ± 1.86 vs 1.85 ± 0.3; p=0.002). Nearly half of the students reported a family history of Diabetes Mellitus (49.2%) and arterial hypertension (52.9%). Near 29% of the participants were overweight and obese. Conclusions: Around 25% of the subjects studied presented 25 OH-Vitamin D deficiency. These subjects, in turn, presented a higher prevalence of hyperinsulinemia and insulin resistance compared with people with normal concentrations of this vitamin. There is also a high prevalence of risk factors among the relatives of the young population that could increase the risk of these students of suffering from Diabetes Mellitus or cardiovascular diseases in the future.

Cross-reactivity, antivenomics, and neutralization of toxic activities of Lachesis venoms by polyspecific and monospecific antivenoms.

BACKGROUND: Bothrops, Crotalus and Lachesis represent the most medically relevant genera of pitvipers in Central and South America. Similarity in venom phenotype and physiopathological profile of envenomings caused by the four nominal Lachesis species led us to hypothesize that an antivenom prepared against venom from any of them may exhibit paraspecificity against all the other congeneric taxa. METHODS: To assess this hypothesis, in this work we have applied antivenomics and immunochemical methods to investigate the immunoreactivity of three monovalent antivenoms and two polyvalent antivenoms towards the venoms from different geographic populations of three different Lachesis species. The ability of the antivenoms to neutralize the proteolytic, hemorrhagic, coagulant, and lethal activities of the seven Lachesis venoms was also investigated. RESULTS: A conspicuous pattern of immunorecognition and cross-neutralization for all effects was evident by the polyspecific antivenoms, indicating large immunoreactive epitope conservation across the genus during more than 10 million years since the Central and South American bushmasters diverged. CONCLUSIONS: Despite the broad geographic distribution of Lachesis, antivenoms against venoms of different species are effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that they can be used equivalently for the clinical treatment of any lachesic envenoming. GENERAL SIGNIFICANCE: This study demonstrates that antivenoms raised against venom of different Lachesis species are indistinctly effective in the neutralization of congeneric venoms not used in the immunization mixture, indicating that antivenoms against conspecific venoms may be used equivalently for the clinical treatment of envenomings caused by any bushmaster species.