Biology subjects

Brito, F.

Publications and source records attributed to Brito, F..

5 recordsLinked to original sources

bioRxiv2025

Correlates of protection against African swine fever virus identified by a systems immunology approach

African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic pigs and wild boars, which poses severe threats to the global pork industry. Despite the promise of live attenuated vaccines (LAVs), their narrow margin between efficacy and residual virulence presents major safety challenges. This study bridges a critical knowledge gap in ASF vaccinology by identifying innate and adaptive correlates of protection. This was achieved by using an established model with two groups of pigs differing in baseline immunological status (farm and specific pathogen-free [SPF]). The animals were immunized with an attenuated ASFV strain and subsequently challenged with a related, highly virulent genotype II strain. By applying a systems immunology approach, we correlated kinetic data, including serum cytokines, blood transcription modules (BTMs), T-cell responses, and antibody levels, with clinical outcomes to track protective and detrimental immune responses to the virus over time. Key innate correlates of protection included early and sustained IFN- response, activation of antigen presentation BTMs, and controlled IL-8 levels during immunization. Lower baseline immune activation observed in SPF pigs in steady state was linked to increased protection. Adaptive correlates encompassed cell cycle, plasma cell, and T-cell BTM responses lasting until day 15 post-immunization. Consequently, an effective response from ASFV-specific Th cells prior to challenge indicated protection. After the challenge, an early IFN- response, along with low levels of pro-inflammatory cytokines and a strong induction of memory Th and Tc cells, correlated with improved clinical outcomes. The model highlights the critical role of host-specific factors in vaccine efficacy and provides a valuable framework for optimizing ASFV vaccine design while distinguishing between protective and detrimental immune responses.

immunology↗

bioRxiv2025

Dendritic-cell diversity in equine blood revealed by single-cell transcriptomics

Unbiased classification of equine dendritic cells (DC) is necessary to address various research questions such as the role of DC subsets in immune-mediated diseases of horses. We applied single-cell RNA sequencing (scRNA-seq) on DC enriched from the blood of two horses. All main DC subsets were detected by key gene expression, including conventional DC type 1 (cDC1; XCR1) and type 2 (cDC2; FCER1A, CD1E) as well as plasmacytoid DC (pDC; TCF4). In addition, we detected a small cluster of hematopoietic progenitors, as well as transitional DC (tDC; FCER1A, TCF4) and putative DC type 3 (DC3; FLT3, CD163). Our data confirms the previously reported phenotype of equine pDC (Flt3+MHC-IIlowCADM1lowCD172aint), cDC1 (Flt3+MHC-IIhighCADM1highCD172alow-int) and cDC2 (Flt3+MHC-IIhighCADM1intCD172ahigh), while also highlighting considerable CD14 expression for cDC2. Two subclusters of equine cDC2 were found to be enriched in FCER1A or CX3CR1 transcripts (cDC2.1 and cDC2.2, respectively), with suggested enhanced extravasation and T-cell stimulatory capacities of the latter. Conservation of DC subsets across species (horse, pig, human, mouse) was illustrated by enrichment analyses with subset-specific gene signatures and by cross-species data integration with publicly available scRNA-seq datasets. Our atlas of equine blood DC is a valuable resource for comparative analyses, and it forms the foundation for understanding the involvement of distinct DC subsets in infections and immune-mediated pathologies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/644174v2_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@bdce22org.highwire.dtl.DTLVardef@1285715org.highwire.dtl.DTLVardef@16d37c8org.highwire.dtl.DTLVardef@1695121_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Unraveling dendritic-cell diversity in blood of pigs: welcome tDC and DC3

Dendritic cells (DC) are professional antigen presenting cells playing a major role in orchestrating adaptative immune responses. To adapt to various immune challenges, such as different classes of pathogens, specialized subsets of DC have evolved across species. To date, DC are classified as conventional DC (cDC1, cDC2) and plasmacytoid DC (pDC), with the more recent addition of DC3 and transitional DC (tDC) that were discovered in human and mouse thanks to high-dimensional phenotyping and single-cell sequencing technologies. Here, by combining flow cytometry and RNA-seq on the bulk- and single-cell level, we identified the porcine equivalent of tDC in blood as CD14-CADM1-CD172a+CD4-cells expressing both Flt3 and CD123 (IL-3RA). This new subset forms a well-defined cluster when mapped onto scRNA-seq data of enriched DC and shares transcriptomic features and abundance with porcine blood cDC2 and pDC. Moreover, we describe putative porcine DC3 as transcriptionally overlapping cells in-between cDC2 and monocytes. With the core functions of tDC and DC3 remaining to be elucidated, our datasets provide a valuable resource for cross-species research on DC heterogeneity in various lymphoid and non-lymphoid tissues.

immunology↗

bioRxiv2022

The temporal regulation inter-leaves from domesticated-tomato contrasts with timelessness of its wild ancestors

Cells, tissues, and organs are characterized by harbouring complex systems allowing communication between one another. Plant domestication was demonstrated to have structured the circadian rhythms, while also synchronising flowering and metabolism. Here, we demonstrate that the domesticated tomato (Solanum lycopersicum) manifests more synchronized rhythmicity across the whole plant. Consequently, the leaf development program is more coordinated in this species than in its wild relatives, wherein S. lycopersicum young leaves develop slowly in comparison to mature leaves. Young leaves from wild tomatoes display higher photosynthesis than mature leaves, while large metabolite accumulations occur across plant segments. Consequently, the diel metabolite levels are rather similar between young and mature leaves in the wild tomato S. pennellii, whereas the expression patterns for circadian clock genes are widely contrasting between both leaves. We further demonstrated that additions of genes related to domestication into the wild tomato S. pimpinellifolium appear to synchronize the development of young and mature leaves to be rather similar to that observed for S. lycopersicum. Collectively, the strengthening of inter-organs relationships on domesticated tomato indicates a synchronized biology, which is most likely fundamental to explaining its elevated yield.

plant biology↗

bioRxiv2019

Novel Rhabdovirus and an almost complete drain fly transcriptome recovered from two independent contaminations of clinical samples.

Metagenomic approaches enable an open exploration of microbial communities without requiring a priori knowledge of a samples composition by shotgun sequencing the total RNA or DNA of the sample. Such an approach is valuable for exploratory diagnostics of novel pathogens in clinical practice. Yet, one may also identify surprising off-target findings. Here we report a mostly complete transcriptome from a drain fly (likely Psychoda alternata) as well as a novel Rhabdovirus-like virus recovered from two independent contaminations of RNA sequencing libraries from clinical samples of cerebral spinal fluid (CSF) and serum, out of a total of 724 libraries sequenced at the same laboratory during a 2-year time span. This drain fly genome shows a considerable divergence from previously sequenced insects, which may obscure common clinical metagenomic analyses not expecting such contaminations. The classification of these contaminant sequences allowed us to identify infected drain flies as the likely origin of the novel Rhabdovirus-like sequence, which could have been erroneously linked to human pathology, had they been ignored.

bioinformatics↗