Ethnic groups can display differential genetic susceptibility to infectious diseases. The arthropod-born viral dengue disease is one such disease, with empirical and limited genetic evidence showing that African ancestry may be protective against the haemorrhagic phenotype. Global ancestry analysis based on high-throughput genotyping in admixed populations can be used to test this hypothesis, while admixture mapping can map candidate protective genes. A Cuban dengue fever cohort was genotyped using a 2.5 million SNP chip. Global ancestry was ascertained through ADMIXTURE and used in a fine-matched corrected association study, while local ancestry was inferred by the RFMix algorithm. The expression of candidate genes was evaluated by RT-PCR in a Cuban dengue patient cohort and gene set enrichment analysis was performed in a Thai dengue transcriptome. OSBPL10 and RXRA candidate genes were identified, with most significant SNPs placed in inferred weak enhancers, promoters and lncRNAs. OSBPL10 had significantly lower expression in Africans than Europeans, while for RXRA several SNPs may differentially regulate its transcription between Africans and Europeans. Their expression was confirmed to change through dengue disease progression in Cuban patients and to vary with disease severity in a Thai transcriptome dataset. These genes interact in the LXR/RXR activation pathway that integrates lipid metabolism and immune functions, being a key player in dengue virus entrance into cells, its replication therein and in cytokine production. Knockdown of OSBPL10 expression in THP-1 cells by two shRNAs followed by DENV2 infection tests led to a significant reduction in DENV replication, being a direct functional proof that the lower OSBPL10 expression profile in Africans protects this ancestry against dengue disease. Dengue is a concern of worldwide health authorities given the increase on virus and vector dispersions. So far only one traditional GWAS survey has been performed in Vietnamese children. This disease is also epidemic in tropical and subtropical regions of the Americas, where most populations descend from a dynamic admixture between African, European and Native American backgrounds. Empirical evidence claimed that African descent was protective against dengue haemorrhagic phenotype in the Cuban population, and this study is the first to apply admixture mapping to identify candidate genes that confer African protection. We also present evidence that two candidate genes, OSBPL10 and RXRA, are differentially expressed along dengue disease progression in Cuban patients and in a Thai dengue transcriptome dataset, and directly show that knockdown of OSBPL10 gene expression leads to a significant reduction in DENV2 replication. A very important overall result of our work is that it provides a unifying framework for many genes that have been said to be protective in dengue. Our evidence places the LXR/RXR activation pathway at the center of natural dengue protection, and supports pursuing therapeutic techniques involving synthetic ligands of nuclear receptor genes or kinases inhibitors that interact with proteins involved in lipid metabolism.

COVID-19 Lethality in Sub-Saharan Africa and Helminth Immune Modulation

The holobiome is an interconnected network of microbial ecosystems spanning soil, plants, animals, humans, and the environment. Microbial interactions drive nutrient cycling, pathogen suppression, and climate regulation. Soil microbiomes facilitate carbon sequestration and enhance soil fertility, while marine microbiomes contribute to carbon capture and climate stability. However, industrial agriculture, extensive herbicide use, antibiotic overuse, and climate change threaten microbial diversity, leading to ecosystem and health disruptions. Probiotic interventions help to restore microbial balance. In human health, probiotics support gut microbiota diversity, reduce inflammation, and regulate metabolism. In agriculture, soil probiotics enhance microbial diversity, improve nutrient cycling, and degrade contaminants, increasing crop yields and soil health. Case studies show that microbial inoculants effectively remediate degraded soils and enhance nutrient uptake. Artificial intelligence is transforming microbiome research by enabling predictive modeling, precision probiotic design, and microbial consortia optimization. Interdisciplinary collaboration and supportive policies are essential for restoring microbial equilibria, ensuring ecosystem resilience, and promoting long-term sustainability. The integration of artificial intelligence, clinical research, and sustainable practices is crucial for advancing holobiome science. The holobiome framework underscores the need for interdisciplinary collaboration to address global challenges, bridging environmental sustainability, agriculture, and public health for a resilient future.

Secondary heterologous dengue infection is a risk factor for severe disease manifestations because of the immune-enhancement phenomenon. Succeeding clinical infections are seldom reported, and the clinical course of tertiary and quaternary dengue infections is not clear. Cuba represents a unique environment to study tertiary/quaternary dengue infections in a population with known clinical and serologic dengue markers and no dengue endemicity. We took advantage of this exceptional epidemiologic condition to study the effect of primary, secondary, tertiary, and quaternary dengue infection exposure on the expression of pro-inflammatory and regulatory cytokines, critical in dengue infection pathogenesis, by using a dengue infection ex vivo model. Whereas secondary exposure induced a high cytokine response, we found a significantly lower expression of tumor necrosis factor-α, interferon-γ, interleukin-10, and tumor growth factor-β after tertiary and quaternary infectious challenge. Significant differences in expression of the cytokines were seen between the dengue immune profiles, suggesting that the sequence in which the immune system encounters serotypes may be important in determining the nature of the immune response to subsequent infections.