Biology subjects

Guerra, J.

Publications and source records attributed to Guerra, J..

5 recordsLinked to original sources

bioRxiv2025

Galectin-1 induces macrophage immunometabolic reprogramming, modulates T cell immunity and attenuates atherosclerotic plaque formation

Background and aimsAtherosclerosis is a chronic immunometabolic disease driven by lipid accumulation and immune cell infiltration. Macrophages and T cells play key roles throughout plaque development. Galectin-1 (Gal-1), a glycan-binding protein, modulates immune functions in these cells and has been reported to attenuate atherosclerosis, though its mechanisms remain incompletely understood. Here, we investigated the effects of Gal-1 on macrophages and T cells during plaque formation. MethodsEffects of Gal-1 on atherosclerosis, macrophages and T cells during lesion formation were studied in Apoe-/- mice treated with recombinant Gal-1. Complementary mouse peritoneal foam cell and in vitro macrophage and T cell cultures experiments were performed to study T cell differentiation, macrophage function, polarization end energy metabolism. The impact of Gal-1 on human macrophages was further evaluated in endarterectomy specimens. ResultsGal-1 treatment reduced lesion size and increased circulating IL-10 levels, inversely correlating with plaque burden. Unexpectedly, IL-10 neutralization also mitigated atherosclerosis, indicating that its action is at least partially IL-10-independent. In plaques, Gal-1 promoted anti-inflammatory macrophage phenotypes, mirrored by a quiescent metabolic and anti-inflammatory profile in foamy macrophages ex vivo. The use of the Gal-1E71Q variant revealed that these effects were only partly dependent on glycan binding. Beyond IL-10, Gal-1 reshaped cytokine profiles by increasing IL-17, IL-22, and IL-23, consistent with a macrophage-driven regulatory Th17 response, alongside higher frequencies of IL-10-producing and regulatory T cells. ConclusionGal-1 protects against atherosclerosis associated with reprogramming macrophages and tuning T cell immunity through glycan-dependent and -independent pathways.

immunology↗

bioRxiv2024

Chronic intermittent fasting impairs β-cell maturation and function in adolescent mice

Intermittent fasting (IF) is a nutritional lifestyle intervention with broad metabolic benefits, but whether the impact of IF depends on the individuals age is unclear. Here, we investigated the effects of IF on systemic metabolism and pancreatic islet function in old, middle-aged, and young mice. Short-term IF improved glucose homeostasis across all age groups, without altering islet function and morphology. In contrast, while chronic IF was beneficial for adult mice, it resulted in impaired {beta}-cell function in the young. Using scRNAseq, we delineated that the {beta}-cell maturation and function score were reduced in young mice. In human islets, a similar pattern was observed in Type 1 (T1D), but not in Type 2 diabetes (T2D), suggesting that the impact of chronic IF in adolescence is linked to the development of {beta}-cell dysfunction. Our study suggests considering the duration of IF in younger people, as it may enhance rather than reduce diabetes outcomes. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=164 SRC="FIGDIR/small/590140v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1676dd1org.highwire.dtl.DTLVardef@15ac993org.highwire.dtl.DTLVardef@167f577org.highwire.dtl.DTLVardef@247e4e_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LILong-term IF impairs {beta}-cell function in adolescent mice. C_LIO_LIIF-induced impaired {beta}-cell function is associated with impaired proliferative capacity and lower levels of mature cells. C_LIO_LIIF-induced impaired {beta}-cell function is associated with a transcriptional change highly conserved in type 1-, but not type 2 diabetes. C_LI

physiology↗

bioRxiv2021

A HYPOMETABOLIC DEFENSE STRATEGY AGAINST PLASMODIUM INFECTION

Hypoglycemia is a clinical hallmark of severe malaria, the often-lethal presentation of Plasmodium falciparum infection of humans. Here we report that mice reduce blood glucose levels in response to Plasmodium infection via a coordinated response whereby labile heme, an alarmin produced via hemolysis, induces anorexia and represses hepatic glucose production (HGP). While protective against unfettered immune-mediated inflammation, organ damage and anemia, when sustained over time heme-driven repression of HGP can progress towards hypoglycemia, compromising host energy expenditure and thermoregulation. This hypometabolic state arrests the development of asexual stages of Plasmodium spp., which undergo pyknosis and develop mitochondrial dysfunction. In response, Plasmodium activates a transcriptional program reducing its virulence and inducing sexual differentiation towards the production of transmissible gametocytes. We infer that malaria-associated hypoglycemia represents a trade-off of an evolutionarily conserved defense strategy restricting Plasmodium spp. from accessing host-derived glucose and balancing parasite virulence and transmission.

immunology↗

bioRxiv2020

Detection of hypermucoviscous Klebsiella pneumoniae sequence type 86 capsular type K2 in South America as an unexpected cause of a fatal outbreak in captivity marmosets

After the sudden death of eleven captives marmosets in a rehabilitation center of wildlife in Sao Paulo, Brazil, histological and microbiological study was conducted. Liver, spleen, intestine, central nervous system, lung, thymus, stomach, testicle tissues were analyzed by light microscopy and microbial cultures were conducted. Environmental cultures were also performed. Prophylactic antimicrobial therapy, restricted access to marmosets cages with dedicated staff, and additional sanitization of animals fruits were implemented. Histological findings were compatible with hyperacute septicemia, and microbiological cultures and molecular tests identified the etiologic agent as hypermucoviscous sequence type 86 capsular type K2 K. pneumoniae for the first time in South America. Implementation of prompt containment measures led to successful control of this outbreak. Detection of a hypervirulent and zoonotic pathogen, such as hypermucoviscous K. pneumoniae ST86 K2, in an unexpected and human interface reservoir underscores its potential threat in public health settings.

microbiology↗

bioRxiv2019

Heme induces innate immunity memory

Trained immunity defines long-lasting adaptive responses of innate immunity, mediated by transcriptional and epigenetic modifications of myeloid cells. Here, we report that labile heme, an alarmin released extracellularily upon tissue damage and hemolysis, induces trained immunity in human and murine primary cells and in mice. Heme-trainning in monocytes is associated with epigenetic and transcriptional profiles that overlap to some extent with those seen in {beta}-glucan-training, the prototype agonist of trained immunity. In sharp contrast to {beta}-glucan training however, heme-training relied on activation of the Syk/JNK-pathway. Heme training in mice was associated with long-lasting expansion of myeloid-biased progenitor cells as well as with altered chromatin accessibility in hematopoietic stem and progenitor cells. Finally, heme-induced training was protective against bacterial sepsis in mice. In conclusion, we reveal that heme, a bona fide alarmin, induces innate immune memory regulating host response to infection.

immunology↗