Biology subjects

Mugnier, M.

Publications and source records attributed to Mugnier, M..

3 recordsLinked to original sources

bioRxiv2026

Restricted expression site use and extreme genome diversification drives trypanosome antigenic variation in chronic bovine infections

Trypanosoma brucei exploits an extreme form of antigenic variation to escape the mammalian immune response. This involves the progressive expression of antigenically distinct variant surface glycoproteins (VSGs) on the surface of individual parasites in the population, generating waves of parasitaemia that are successively cleared by host antibodies. Current paradigms were established using in vitro studies and acute rodent infections characterized by high parasitaemia, but natural livestock infections are characterized by low parasitaemia and chronicity. Here, we analysed the infection dynamics of isogenic parasites in mice and cattle in blood during early and chronic infections, quantitating VSG expression diversity within and between hosts, antigen type persistence in vivo and their timing of appearance. This revealed enhanced antigenic diversity in cattle but with a surprisingly reproducible temporal expression hierarchy of related VSGs between independent chronic infections. Analyses demonstrated the unexpected dominance of a single telomeric VSG expression site irrespective of host species and time of infection. Detailed prediction of mosaic VSG assembly reveals exceptional parasite genome diversification within infections involving extensive macro and micro-homology-based recombination to evolve the antigen repertoire. This diversity was restricted but not eliminated in homologous recombination mutants, which could nonetheless sustain chronic infections in mice. These data provide the first comprehensive insight into trypanosome antigenic variation in the clinically-relevant host.

microbiology↗

bioRxiv2026

Maternal Trypanosoma cruzi infection is associated with significant placental remodeling regardless of vertical transmission

Chagas disease is a major protozoan infection in the Americas, causing approximately 12,000 deaths each year. It is caused by Trypanosoma cruzi, and can be transmitted transplacentally, leading to congenital Chagas disease, a silent route that carries substantial risk for newborns. However, the mechanisms underlying congenital Chagas transmission are poorly understood. Here, we evaluated whether T. cruzi infection alters the placental microenvironment and systemic physiology, and whether such alterations are associated with congenital transmission. Integrating bulk RNA sequencing, proteomics, and spatial transcriptomics, we show that T. cruzi infection elicits profound molecular remodeling in both placenta and peripheral blood, regardless of transmission status. Transmitting mothers exhibit a distinct transcriptional signature enriched for inflammatory and tissue-remodeling pathways. Notably, peripheral blood profiles mirrored some placental alterations. A panel of inflammatory serum proteins showed promising predictive potential for transmission risk, with implications for prenatal monitoring. Together, these findings support a fundamental shift in the conceptual framework of congenital Chagas disease, from a transmission-centered model to one that recognizes infection-driven placental damage as a pathological spectrum and identifies peripheral blood as a promising, non-invasive source of predictive biomarkers for adverse pregnancy outcomes. This framework motivates the further application of single-cell-resolution approaches to refine models of congenital Chagas pathogenesis and the systematic analysis of maternal peripheral blood during pregnancy to enable early risk stratification and the development of predictive tools for adverse outcomes.

molecular biology↗

bioRxiv2023

A murine model of Trypanosoma brucei-induced myocarditis and cardiac dysfunction

Trypanosoma brucei is a protozoan parasite that causes human and animal African trypanosomiases (HAT and AAT). Cardiac symptoms are commonly reported in HAT patients, and intracardiac parasites with accompanying myocarditis have been observed in both natural hosts and animal models of T. brucei infection. Despite the importance of T. brucei as a cause of cardiac dysfunction and the dramatic socioeconomic impact of African trypanosomiases in sub-Saharan Africa, there are currently no reproducible murine models of T. brucei-associated cardiomyopathy. We present the first clinically relevant, reproducible murine model of cardiac dysfunction in chronic T. brucei infection. Similar to humans, mice showed histological evidence of myocarditis and elevation of serum NT-proBNP with electrocardiographic abnormalities. Serum NT-proBNP levels were elevated prior to the development of severe ventricular dysfunction. On flow cytometry, myocarditis was associated with an increase of most myocardial immune cell populations, including multiple T cell and macrophage subsets, corroborating the notion that T. brucei-associated cardiac damage is an immune-mediated event. This novel mouse model represents a powerful and practical tool to investigate the pathogenesis of T. brucei-mediated heart damage and supports the development of therapeutic options for T. brucei-associated cardiac disease.

microbiology↗