Biology subjects

Malleret, B.

Publications and source records attributed to Malleret, B..

4 recordsLinked to original sources

bioRxiv2026

MaRNAV-1 infection of Plasmodium vivax is associated with increased parasite transmission and host inflammatory responses

MaRNAV-1 is an RNA virus recently identified in Plasmodium vivax-infected samples, but definitive evidence that it infects the parasite and influences malaria pathogenesis remains unknown. Here, we demonstrate that MaRNAV-1 is an intracellular virus that is present in P. vivax at various stages of its life cycle, including blood, sporozoite, and liver stages. Viral prevalence varied geographically between Cambodian and Ethiopian parasites. MaRNAV-1 presence and load were positively associated with parasite transmission potential, as reflected by increased gametocyte abundance and higher oocyst prevalence and intensity in membrane feeding assays. MaRNAV-1 loads were higher in symptomatic compared to asymptomatic infections, and higher MaRNAV-1 loads were associated with elevated body temperature, independently of parasitemia. MaRNAV-1 infection elicits an antibody response and is associated with dendritic cell activation, a shift from Th2 to a Th1-driven immune response, and an increased frequency of double-negative B cells. Accordingly, MaRNAV-1-infected patients had higher concentrations of circulating cytokines, such as IFN-{gamma}, CXCL10, IL-1RA, and IL-6, independently of parasitemia. Together, these findings demonstrate that MaRNAV-1 is a genuine parasite-infecting virus associated with increased parasite transmission potential and with modulation of clinical outcomes in, and host immune response to, P. vivax infections. Our study broadens the conventional view of host-pathogen interactions in malaria by revealing complex virus-parasite-host relationships.

microbiology↗

bioRxiv2025

Hidden hematological, biochemical and immune costs of asymptomatic malaria infections in semi-wild chimpanzees

The health consequences of Plasmodium infections in wild great apes, particularly in asymptomatic animals, remain poorly understood. This study investigated the hematological and immune impacts of natural malaria infections in 27 semi-wild chimpanzees (Pan troglodytes troglodytes) from Gabon. Using MinION sequencing and species-specific PCR, results showed a 48.15% overall Plasmodium infection rate, with frequent multi-species co-infections involving Plasmodium gaboni, Plasmodium reichenowi, and Plasmodium vivax-like parasites. In addition, younger animals were significantly more infected and exhibited higher parasitemia levels, especially those with triple infections involving P. vivax-like. Profiling of 15 hematological markers and 8 cytokines/chemokines known to be associated with malarial infections in humans revealed significant alterations in infected chimpanzees, including elevated urea, reduced creatinine, and increased systemic concentrations of pro-inflammatory (TNF, IL-1{beta}, CCL3) and anti-inflammatory (IL-10) cytokines. Ex vivo PBMC stimulation yielded higher IL-10 in infected than non-infected individuals, indicating a regulatory-skewed cytokine response at the time of sampling. These results suggest that malaria in chimpanzees is associated with systemic immune modulation and accompanied by signs of physiological stress, including potential renal dysfunction. This study challenges the assumption that chronic Plasmodium infections are entirely benign in great apes and highlight the need to integrate immunological health indicators into conservation strategies. Broader immune profiling and longitudinal studies will be essential in the future to assess long-term health outcomes and resilience in these endangered populations.

evolutionary biology↗

bioRxiv2023

The artemisinin-induced dormant stages of Plasmodium falciparum exhibit hallmarks of cellular senescence and drug resilience.

Recrudescent infections with human malaria parasite, Plasmodium falciparum, presented traditionally the major setback of artemisinin-based monotherapies. Although introduction of artemisinin combination therapies (ACT) largely solved the problem, the ability of artemisinin to induce dormant parasites still poses major obstacle for current as well as future malaria chemotherapeutics. Here, we developed a robust laboratory model for induction of dormant P. falciparum parasites and characterized their transcriptome, drug sensitivity profile and cellular ultrastructure. We show that P. falciparum dormancy requires a ~5-days maturation process during which the genome-wide gene expression pattern gradually transitions from the ring-like state to a highly unique form. The transcriptome of the mature dormant stage carries hallmarks of cellular senescence with downregulation of most cellular functions associated with growth and development, but upregulation of selected metabolic functions and DNA repair. Moreover, the P. falciparum dormant stage is considerably more resistant to essentially all antimalaria drugs compared to the fast-growing asexual stages. Finally, the unique cellular ultrastructure further suggests unique properties of this new developmental stage of the P. falciparum life cycle that should be taken into consideration by new malaria control strategies.

microbiology↗

bioRxiv2023

Chloroquine induces eryptosis in P. falciparum-infected red blood cells and the release of extracellular vesicles with a unique protein profile

Malaria is a vector-borne parasitic disease that affects millions worldwide. In order to reach the objective, set by the World Health Organization to decrease the cases by 2030, antimalarial drugs with novel modes of action are required. Previously, a novel mechanism of action of chloroquine (CQ) was reported involving features of programmed cell death in the parasite, mainly characterized by calcium efflux from the digestive vacuole (DV) permeabilization. Increased intracellular calcium induces the suicidal death of erythrocytes also known as eryptosis. This study aimed to identify the hallmarks of eryptosis due to calcium redistribution and the downstream cellular effects during CQ treatment in iRBCs. Plasmodium falciparum 3D7 at mid-late trophozoites were used for the antimalarial drug treatment. Our results revealed increased phosphatidylserine (PS) exposure, cell shrinkage and membrane blebbing, delineating an eryptotic phenotype in the host RBC. Interestingly, the blebs on the surface of the iRBCs released to the extracellular milieu become extracellular vesicles (EVs) which are essential for intercellular communication due to their cargo of proteins, nucleic acids, lipids and metabolites. The proteomic characterization displayed 2 highly enriched protein clusters in EVs from CQ-treated iRBCs, the proteasome and ribosome. We demonstrated that this unique protein cargo is not associated with the parasite growth rate. Additionally, we found that these particular EVs might activate IFN signaling pathways mediated by IL-6 in THP-1-derived macrophages. Our findings shed new insights into a novel drug-induced cell death mechanism that targets the parasite and specific components of the infected host RBC. IMPORTANCEOur previous studies have shown that chloroquine (CQ) treatment in iRBCs triggers Plasmodium falciparum digestive vacuole (DV) membrane permeabilization leading to calcium redistribution. Interestingly, increased intracellular calcium concentration is the main inducer of the suicidal death of red blood cells (RBCs) called eryptosis. The present study shed new insights into a novel CQ-induced cell death mechanism that targets the parasite and the infected host RBC by inducing key phenotypic hallmarks of eryptosis: PS exposure, cell shrinkage and membrane blebbing. Moreover, the proteomic characterization of the blebs released to the extracellular milieu also known as extracellular vesicles (EVs) revealed a cargo highly enriched in ribosomal proteins and proteasome subunits relevant for host-parasite interactions. These findings highlight CQs effect on calcium homeostasis disruption in infected red blood cells (iRBCs) with cellular and immunological consequences of great significance for malaria pathogenesis and potential clinical implications.

cell biology↗