Biology subjects

Rijo-Ferreira, F.

Publications and source records attributed to Rijo-Ferreira, F..

4 recordsLinked to original sources

bioRxiv2026

Ascorbate and TET2 couple balanced hematopoiesis to disease tolerance

Infections stimulate myelopoiesis but this comes at the cost of reduced production of other lineages. It is unclear if this imbalance is protective or damaging, and if factors that promote balanced hematopoiesis can impact infection pathology. Here we show that the ascorbate-TET axis limits excessive myelopoiesis, promotes balanced hematopoiesis, and is essential for surviving malaria. Hematopoietic-specific ascorbate depletion promoted myelopoiesis. The effects of ascorbate were mediated by TET2/TET3 activity in myeloid progenitors. Combined ascorbate and TET2 depletion markedly skewed hematopoiesis to the myeloid lineage and impaired erythropoiesis. Ascorbate is commonly depleted in infections, but the functional significance of this remains unclear. In the absence of ascorbate and TET2, mice infected with Plasmodium parasites could clear the pathogen, but had exacerbated myeloid and impaired erythroid response, anemia, and tissue damage and they succumbed to infection, indicating compromised disease tolerance. Therefore ascorbate and TET2 promote balanced hematopoiesis to impart tolerance to malaria.

immunology↗

bioRxiv2026

PlasmoRhythm: A comprehensive database for malaria-associated rhythmic transcripts, proteins, and metabolites

Abstract: Motivation: The malaria transmission cycle is temporally organized across three interacting biological systems: the parasite, vertebrate host, and mosquito vector. Rhythms in parasite development, host physiology, and vector behavior govern infection dynamics, transmission, and the efficacy of stage-specific antimalarial interventions. However, the molecular architecture connecting these rhythms remains difficult to interrogate because time-resolved omics datasets are distributed across species, experimental paradigms, and analytical frameworks, with no unified resource for comparative analysis. Results: We developed PlasmoRhythm, a curated database integrating 67 transcriptomic, proteomic, and metabolomic datasets from 15 studies, encompassing 1,126 sampling events across Plasmodium species, mammalian hosts, and Anopheles vectors. Harmonized metadata and rhythmicity outputs from JTK_CYCLE, ARSER, Lomb-Scargle, and the meta2d function support interactive cross-study interrogation of molecular profiles. Dedicated modules enable the exploration of rhythmic virulence factors and antimalarial drug interactors, providing a unified framework for hypothesis generation across the malaria transmission cycle. Availability: PlasmoRhythm is freely accessible at https://project.iith.ac.in/cgntlab/PlasmoRhythm/.

bioinformatics↗

bioRxiv2024

Circadian rhythms mediate malaria transmission potential

Malaria transmission begins when infected female Anopheles mosquitos deposit Plasmodium parasites into the mammalian hosts skin during a bloodmeal. The salivary gland-resident sporozoite parasites migrate to the bloodstream, subsequently invading and replicating within hepatocytes. As Anopheles mosquitos are more active at night, with a 24-hour rhythm, we investigated whether their salivary glands are under circadian control, anticipating bloodmeals and modulating sporozoite biology for host encounters. Here we show that approximately half of the mosquito salivary gland transcriptome, particularly genes essential for efficient bloodmeals such as anti-blood clotting factors, exhibits circadian rhythmic expression. Furthermore, we demonstrate that mosquitoes prefer to feed during nighttime, with the amount of blood ingested varying cyclically throughout the day. Notably, we show a substantial subset of the sporozoite transcriptome cycling throughout the day. These include genes involved in parasite motility, potentially modulating the ability to initiate infection at different times of day. Thus, although sporozoites are typically considered quiescent, our results demonstrate their transcriptional activity, revealing robust daily rhythms of gene expression. Our findings suggest a circadian evolutionary relationship between the vector, parasite and mammalian host that together modulate malaria transmission.

microbiology↗

bioRxiv2022

Extravascular spaces are reservoirs of antigenic diversity in Trypanosoma brucei infection

Summary paragraphThe protozoan parasite Trypanosoma brucei evades clearance by the host immune system through antigenic variation of its dense variant surface glycoprotein (VSG) coat, periodically "switching" expression of the VSG using a large genomic repertoire of VSG-encoding genes1-6. Recent studies of antigenic variation in vivo have focused near exclusively on parasites in the bloodstream4,7,8, but research has shown that many, if not most, parasites reside in the interstitial spaces of tissues9-13. We sought to explore the dynamics of antigenic variation in extravascular parasite populations using VSG-seq7, a high-throughput sequencing approach for profiling VSGs expressed in populations of T. brucei. Here we show that tissues, not the blood, are the primary reservoir of antigenic diversity during both needle- and tsetse bite-initiated T. brucei infections, with more than 75% of VSGs found exclusively within extravascular spaces. We found that this increased diversity is correlated with slower parasite clearance in tissue spaces. Together, these data support a model in which the slower immune response in extravascular spaces provides more time to generate the antigenic diversity needed to maintain a chronic infection. Our findings reveal the important role that extravascular spaces can play in pathogen diversification.

microbiology↗