Ribeiro, M. S. | Search bioRxiv

bioRxiv2025

CD39 REGULATES P2RX7-MEDIATED LUNG NECROTIC LESIONS IN SEVERE EXPERIMENTAL TUBERCULOSIS

Tuberculosis induces diverse lesions, such as necrotic pneumonia, contributing to disease progression and transmission. Despite advances in understanding the role of ATP-gated P2RX7 ion channels in developing severe forms of tuberculosis, the regulation of this important signaling pathway remains unclear. Herein, we show that the ectonucleotidase CD39 plays an essential regulatory role in TB progression by preventing lung tissue damage, bacterial dissemination, and excessive inflammatory responses. Mechanistically, through its enzymatic activity on the cellular surface, CD39 protects infected macrophages from undergoing necrotic death mediated by P2RX7 activation. We proposed that by protecting macrophages from P2RX7-mediated cell death and bacterial dissemination, CD39 prevents the development of necrotic lesions. Altogether, these findings uncover a significant role for CD39 as an essential component of the molecular regulation underlying the development of severe tuberculosis. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/656614v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1dc7320org.highwire.dtl.DTLVardef@a4202org.highwire.dtl.DTLVardef@173bb62org.highwire.dtl.DTLVardef@1132f0f_HPS_FORMAT_FIGEXP M_FIG C_FIG BriefIn tuberculosis, necrotic granuloma-like structures release extracellular ATP (eATP), which triggers P2RX7-mediated immune cell death. CD39 degrades eATP, preventing P2RX7 activation and promoting macrophage survival, thereby limiting inflammation, tissue damage, and bacterial dissemination.

immunology↗

bioRxiv2023

Do you have enough space? Habitat selection of insectivorous cave-dwelling bats in fragmented landscapes of Eastern Amazon

Individual movements of bats result from a compromise between their recognition of the environment and their potential to fulfill bats life requirements, and to the potential threats associated with moving, all of this is mediated by habitat selection. Mining activities produce modifications to the environments that add heterogeneity and fragmentation to the landscapes used by bats, with overall poorly understood consequences to their movements and to the underground-related biodiversity. Cave dwelling bats spend a large part of their life cycle within their roosts, and they are of paramount importance to the subterranean biodiversity because of their constant movements between the external landscapes, which they selectively use, and the underground ecosystems, where they usually apport energy in form of organic matter. We investigated the variation of patterns of habitat use and selection by cave-dwelling bats in a mosaic of disturbed and conserved Eastern Amazonian forests and rupestrian iron-rich savannas (cangas) interspersed in an extensive iron-caves system. We studied the movements of two phylogenetically distant related insectivores, the aerial insect-catcher Furipterus horrens (Furipteridae) and the foliage gleaning bat Lonchorhina aurita (Phyllostomidae), both cave-dependent in the study area, one of them categorized as threatened to extinction in Brazil, and virtually unknown in terms of their movement behavior, and habitat use. We used radio telemetry to assess habitat use, under the prediction that these species prefer natural and conserved habitats for their foraging bouts, avoiding human-modified habitats. We also anticipated larger range-areas and commuting distances for both species when foraging in disturbed landscapes. Thirty-one bats were monitored in different landscapes (conserved Amazonian ombrophilous forests and cangas, mining sites and pasture) resulting in an average range of 346.9 {+/-} 762.5 ha and an average commuting distance of 1921.5 {+/-} 2269.7 m for F. horrens and of 716.8 {+/-} 1000.6 ha and 2582.2 {+/-} 1966.0 m for L. aurita. Our habitat selection analyses suggest that Furipterus horrens is an open space forager, with individuals frequently recorded foraging in cangas, and L. aurita is a forest forager, although using all habitats proportionally to their availability in the landscape. We did not detect landscape-related effects to the use of space by both species, whereas seasonal variation emerged as a relevant effect. This is the first time that movement data for F. horrens and L. aurita is presented. Our study delivers original baseline data on movement behavior and conservation of these threatened cave-dwelling bat species with virtually unknown biology and shed light into constraints related to the optimal and adjusted biological cycles of the bats and their range areas under scenarios of disturbance.

ecology↗

bioRxiv2017

Genomic and structural features of the Yellow Fever virus from the 2016-2017 Brazilian outbreak

Brazil has been suffering a severe sylvatic epidemic of yellow fever virus (YFV) since late 2016. Analysis of full-length YFV genomes from all hosts involved in the Brazilian 2017 outbreak reveals that they belong to sub-lineage 1E within modern-lineage, but display several unique amino acid substitutions in highly conserved positions at NS3 and NS5 viral proteins. Evolutionary analyses indicate that YFV carrying that set of amino acid substitution circulates in the Southern Brazilian region for several months before being detected in December 2016. Structural and selection analyses support that some of these substitutions were under positive selection and could impact enzyme structure and function. Altogether, this evidence demonstrated that the current Brazilian YFV carries unique amino acid signatures in the non-structural proteins and support the hypothesis that those substitutions may be affecting the viral fitness and transmissibility.

microbiology↗