Biology subjects

Salazar, F.

Publications and source records attributed to Salazar, F..

7 recordsLinked to original sources

bioRxiv2026

A murine model to study chronic airway fungal colonisation that recapitulates human disease

Aspergillus fumigatus is a ubiquitous environmental mould and a leading cause of chronic fungal-associated respiratory disease, yet the mechanisms by which persistent airway colonisation drives immune adaptation and lung pathology remain poorly understood. Progress in this area has been limited by the lack of in vivo models that recapitulate stable, non-invasive fungal persistence without immunosuppression. Here, we developed and optimised a murine model of chronic airway colonisation using agar bead-embedded A. fumigatus conidia delivered intratracheally. Embedding did not impair fungal germination or hyphal growth, and the agar matrix was immunologically inert, supporting its use as a neutral scaffold. This approach established stable fungal persistence in the airways for at least three weeks in immunocompetent mice without inducing invasive disease or systemic morbidity. Colonisation elicited a transient, airway-restricted innate immune response characterised by early neutrophil and monocyte recruitment and increased CXCL1, MIP-1, MIP-1{beta}, and TNF production, which resolved over time. Histopathological analysis revealed a progressive sequence of disease-relevant features, including initial immune containment, followed by mucus hypersecretion, and airway remodelling. At the adaptive level, persistent colonisation induced a dynamic T cell response that transitioned from an early polyfunctional profile to a sustained Th17-dominant phenotype. Importantly, application of this model in CFTR-deficient mice uncovered enhanced collagen deposition and fibrotic remodelling without altered fungal burden, demonstrating its utility in modelling disease-relevant outcomes in susceptible hosts. Together, this study establishes a robust and physiologically relevant platform for investigating host-fungal interactions during chronic airway colonisation. This model provides new opportunities to dissect mechanisms of immune adaptation, fungal persistence, and tissue remodelling, and to identify therapeutic strategies targeting chronic Aspergillus-associated lung disease.

immunology↗

bioRxiv2026

Dectin-2-dependent adaptive immunity governs intestinal clearance of systemic Candida albicans

Effective immunity to Candida albicans requires coordination between innate recognition and induction of adaptive CD4 T cell responses. While the C-type lectin receptor Clec4n (Dectin-2) is known to drive Th17 polarization, its role in shaping tissue-specific adaptive responses remains incompletely understood. Here, we used an OT-II antigen-specific CD4 T cell transfer model combined with OVA-expressing Candida albicans to dissect the function of Dectin-2 during systemic infection. We found that Dectin-2 is dispensable for antigen presentation and CD4 T cell priming in gut-draining lymph nodes. Moreover, we show that Dectin-2-deficient mice fail to control fungal growth in the intestinal mucosa, despite elevated local production of IL-17A and GM-CSF. The increased susceptibility of the Dectin-2-deficient mice was associated with impaired neutrophil activation in the intestinal mucosa. These findings identify a tissue-specific checkpoint role for Dectin-2, linking balanced adaptive Th17 cytokine responses to granulocyte function, and revealing a previously unappreciated mechanism required for anti-fungal immune regulation at intestinal mucosal surface.

immunology↗

bioRxiv2025

Clec7a-mediated regulation of Killer-like Lectin Receptor expression controls T cell immunity

Clec7a is a C-type lectin receptor (CLR) originally defined for its non-redundant role in anti-fungal immunity. Subsequent work has broadened this view, implicating Clec7a in host defense against diverse pathogens and in the pathogenesis of cancer, autoimmunity, neuroinflammation, and developmental disorders. How a single innate receptor orchestrates such wide-ranging outcomes remains unresolved. We previously demonstrated that dendritic cell (DC)-expressed Clec7a is required for protective anti-fungal immunity in the gastrointestinal tract through regulation of fungus-specific CD4 T cell responses. Here, we show that Clec7a controls the expression of multiple C-type lectins in DCs, including a cluster of killer lectin-like receptors (KLRs). Notably, we reveal that these KLRs directly regulate DC function and control CD4 T cell responses. These findings define a novel Clec7a-KLR axis that integrates innate and adaptive immunity, highlighting a regulatory pathway with broad relevance for immune homeostasis, inflammation, and host defense.

immunology↗

bioRxiv2025

Pairing extinction training with vagus nerve stimulation (VNS) reduces drug-seeking by altering activity in afferents to the medial prefrontal cortex

Relapse triggered by drug-associated cues or stress remains a major challenge in treating substance use disorders (SUDs), as re-exposure reliably provokes craving and reinstatement of drug seeking. Extinction-based interventions can reduce cue reactivity, yet extinction learning is often weak or context-dependent, limiting its clinical impact. Vagus nerve stimulation (VNS) enhances learning-related plasticity via widespread engagement of neuromodulatory systems and cortical circuits. Recent preclinical work shows that pairing extinction with VNS facilitates extinction learning and reduces cue-induced reinstatement of cocaine seeking, suggesting translational potential as an adjunct to exposure-based therapies. However, the circuit-level mechanisms underlying these effects remain unclear. To address this gap, we examined how VNS paired with extinction alters activity in medial prefrontal cortex (mPFC) networks that regulate drug seeking, focusing specifically on afferent projections from the basolateral amygdala (BLA) and ventral hippocampus (vHPC). Male rats received retrograde AAV-eGFP infusions into either the prelimbic (PL) or infralimbic (IL) cortex to label upstream projections, followed by cocaine self-administration, extinction training with VNS or sham stimulation, and cue-induced reinstatement. cFos immunolabeling in the BLA and vHPC revealed pathwayspecific modulation: VNS decreased overall BLA activity and reduced activation of BLA to IL projections, but increased activation of BLA to PL projections. In the vHPC, VNS selectively decreased activation of vHPC to IL projections without affecting PL-projecting neurons. Because these pathways synapse onto parvalbumin interneurons (PVIs) in the mPFC, we quantified PVI activation and found that VNS decreased overall prefrontal cFos expression, but increased PVI activity in the PL, and decreased PVI activity in the IL. Together, these results demonstrate that VNS paired with extinction reshapes prefrontal-amygdala-hippocampal circuits in a pathway-specific manner, potentially modulating feed-forward inhibition to reduce relapse-like behavior. These findings support VNS as a promising strategy to strengthen extinction learning and improve treatment outcomes in SUD.

neuroscience↗

bioRxiv2025

Guardians of the canopy: two new turtle ant species (Hymenoptera: Formicidae: Cephalotes), from Ecuador Choco and Amazonia, revealed by morphology and DNA barcoding

We describe two new species of arboreal ants of the genus Cephalotes Latreille, 1802, from Ecuador: Cephalotes esthelae Ilguan & Troya, sp. nov. and Cephalotes sacha Yumbay & Troya, sp. nov. The former, a member of the grandinosus-group, was collected from lowland Choco and Amazonian forests, while the latter, belonging to the atratus-group, is an inhabitant of the Amazonian region, including Yasuni National Park. Diagnoses and detailed morphological descriptions of workers and soldiers are provided, illustrated by high-resolution images. Species identification was further corroborated with mitochondrial CO1 sequences, which confirmed their distinctiveness from morphologically similar congeners. Both species exhibit unique combinations of mesosomal and gastric characters. In addition, we provide the first description of the soldier of the rarely collected C. dentidorsum De Andrade, 1999. These discoveries expand the known diversity of the genus in Ecuador to 33 species, highlighting this regions role as a hotspot for Neotropical myrmecofauna. A fully illustrated key and checklist of all Cephalotes species known from Ecuador is also presented. The new taxa occur in well-preserved but increasingly threatened forests, ecosystems subject to high rates of deforestation and mining activity, potentially endangering their populations. The integration of molecular and morphological evidence provides a robust framework for delimiting species such as in this morphologically complex and species-diverse genus. We highlight the need of further exploration of under-collected regions such as the Choco and Andean-Amazonian foothills. Continued taxonomic and molecular investigations will be crucial to elucidate phylogenetic relationships, assess biogeographic barriers such as the Andes, and inform conservation strategies for Ecuadors arboreal ant fauna.

zoology↗

bioRxiv2025

KLRE1 shapes antifungal immunity by tuning dendritic cell and T cell activation through distinct heterodimeric partners

Dendritic cells (DCs) instruct adaptive immunity by integrating inflammatory cues to regulate co-signalling molecules and T cell activation. We recently discovered that the pattern recognition receptor Dectin-1 (Clec7a) controls expression of a network of killer lectin-like receptors (KLRs), including KLRI1 and KLRI2, which regulate adaptive immune responses. Here, we identify KLRE1 as a key regulator of DC phenotype and function, acting through distinct heterodimeric interactions with KLRI1 and KLRI2. KLRE1 is expressed by tissue-resident and bone marrow-derived DCs and is dynamically regulated by inflammatory signals, including fungal stimuli. Mechanistically, KLRE1:KLRI1 heterodimers promote DC activation, increasing CD40, CD80, CD86, and MHC-II, whereas KLRE1:KLRI2 heterodimers restrain activation. Differential regulation of KLRI1 and KLRI2 by inflammatory signals shapes heterodimer availability and immune outcomes under distinct conditions. Functionally, KLRE1 deficiency enhances DC activation and T cell responses in vitro and in vivo during Candida albicans infection. Strikingly, KLRI1- and KLRI2-deficient mice showed opposite survival outcomes during systemic candidiasis, despite similar fungal burdens, implicating KLRE1 heterodimers in disease tolerance rather than pathogen clearance. Protection in KLRI1-deficient mice was associated with a more balanced T cell response, whereas susceptibility to infection associated with KLRI2 deficiency resulted from increased T cell activation and migratory potential, leading to systemic inflammation and renal dysfunction. Thus, KLRE1 heterodimers fine-tune DC-driven T cell immunity, balancing protection and immunopathology during fungal infection.

immunology↗

bioRxiv2022

Global mosquito virome profiling and mosquito spatial diffusion pathways revealed by marker-viruses

Mosquitoes are vectors of numerous emergence and reemergence of mosquito-borne diseases, leading to an overwhelming global challenge. The boom in metagenomic studies promoted the increase of mosquito viruses being described, and studies from different regions of the world showed that mosquitoes harbor abundant and diverse viromes. However, there is still a lack of large-scale systematic comparison of viromes among various ecological factors such as the mosquito species/genera, location, etc, and consistent patterns associated with these factors are not clear. Here, we provide an overview of virome profiling that integrated the perspective of mosquito genus, locations, and climates based on the global scale, and redefined the core-virome. Our results also further implicate some mosquito-associated viruses strongly associated with the ecological factors and highlighted the evidence of mosquitoes cross-regional movements by the candidate marker viruses. The study may be helpful in gaining new insights into strategies to prevent arbovirus epidemics.

microbiology↗