Biology subjects

Cortes-Selva, D.

Publications and source records attributed to Cortes-Selva, D..

3 recordsLinked to original sources

bioRxiv2025

Schistosoma mansoni antigen induced innate immune memory features mitochondrial biogenesis and can be inhibited by ovarian produced hormones

We have previously identified that S. mansoni infection induces a unique form of myeloid training that protects male but not female mice from high fat diet induced disease. Here we demonstrate that ovarian derived hormones account for this sex specific difference. Ovariectomy of females prior to infection permits metabolic reprogramming of the myeloid lineage, with BMDM exhibiting carbon source flexibility for cellular respiration, and mice protected from systemic metabolic disease. The innate training phenotype of infection can be replicated by in vivo injection of SEA, and by exposure of bone marrow to SEA in culture prior to macrophage differentiation (Day 0). This protective phenotype is linked to increased chromatin accessibility of lipid and mitochondrial pathways in BMDM including Nrf1 and Tfam, as well as mitochondrial biogenesis. This work provides evidence that S. mansoni antigens induce a unique form of innate training inhibited by ovarian-derived hormones in females.

immunology↗

bioRxiv2020

Maternal schistosomiasis impairs offspring IL-4 production and B cell expansion

Maternal helminth infections are a global public health concern and correlate with altered infant immune responses to some childhood immunizations, but a mechanistic understanding of how maternal helminth infection alters the cellular immune responses of offspring is lacking. Here we establish a model of maternal Schistosoma mansoni infection in dual IL-4 reporter mice. We find that offspring born to mothers infected with S. mansoni have impaired production of IL-4 during homoeostasis, and following immunization with a Tetanus-Diphtheria vaccine. We identified that iNKT cells are the dominant source of IL-4 during early life homeostasis, and that diminished IL-4 production was associated with both reduced B cell and follicular dendritic cell responses. These defects were maintained long-term, affecting memory B and T cell responses. Single-cell RNASeq analysis of immunized offspring identified egg antigen-dependent reductions in B-cell cell cycle and proliferation-related genes. These data reveal that maternal infection leads to long-lasting defects in the cellular responses to heterologous antigens and provide vital insight into the influence of maternal infection on offspring immunity.

immunology↗

bioRxiv2020

Schistosoma mansoni infection induces long-lived sex-specific metabolic reprogramming of the myeloid lineage

Despite evidence that helminths protect from metabolic disease, a major gap exists in understanding the underlying mechanism(s). Here we demonstrate that bone marrow derived macrophages (BMDM) from S. mansoni infected male ApoE-/- mice have dramatically increased mitochondrial respiration compared to those from uninfected mice. This change associates with increased glucose and palmitate shuttling into TCA cycle intermediates and decreased accumulation of cellular cholesterol esters. Moreover, systemic metabolic modulation by schistosomes is a function of biological sex, where infection protects ApoE-/- male, but not female, mice from obesity and glucose intolerance. Sex-dependence extends to myeloid cells, where reprogramming leads to opposite cholesterol phenotypes in BMDM from females and males. Finally, the metabolic reprogramming of male myeloid cells is transferrable via bone marrow transplantation to an uninfected host, indicating maintenance of reprogramming in the absence of sustained antigen exposure. This work reveals that S. mansoni systemic reprograming of myeloid metabolism is sex-dependent.

immunology↗