Biology subjects

da Costa, R.

Publications and source records attributed to da Costa, R..

5 recordsLinked to original sources

bioRxiv2026

A Genetic Tool for Specific Tracking of Mature Neutrophils

Tracking mature neutrophils remains challenging due to the lack of reliable cell surface markers. Although CD101 is a promising candidate for mature neutrophils, its stability under pathological conditions is unclear. Using a CD101-tdTomato reporter mouse model, we confirmed that the reporting system does not alter CD101 expression, and tdTomato fluorescence is predominantly expressed in mature neutrophils across peripheral tissues. Further analysis revealed that CD101+ and tdTomato+ neutrophils display identical characteristics of mature neutrophil, including poly-segmented nuclei, cell size, and key functions under homeostasis. By comparing tdTomato fluorescence with CD101 protein levels, we demonstrate that reduced CD101 expression under pathological states was not attributed to shedding or degradation. Our finding enhances CD101 as a robust and reliable marker of neutrophil maturity, providing a foundation for future applications in spatial transcriptomics and lineage tracing studies to dissect neutrophil heterogeneity and function. Highlights of the studyO_LIIn CD101-tdTomato homozygous mice, tdTomato is predominantly expressed in neutrophils and labels nearly 100% of mature neutrophils, aligning with the phenotype of CD101+ mature neutrophils; C_LIO_LIThe CD101-tdTomato reporting system does not interrupt CD101 expression or neutrophil functions; C_LIO_LICD101 remains a stable and reliable cell surface marker for labeling mature neutrophils, even under pathological conditions. C_LI

immunology↗

bioRxiv2026

Acute IFN-gamma responses drive sensory neuron injury and chronic pain after chikungunya virus infection

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute and chronic musculoskeletal disease characterized by often debilitating pain; however, the mechanisms associated with the pain remain understudied. Here, we used an experimental mouse model and patients to investigate the role of interferon-{gamma} (IFN-{gamma}) in the pain during chronic inflammation after CHIKV infection. Our data show that CHIKV induces sustained joint inflammation, cartilage catabolism, and sensory neuron injury signatures, including Atf3 upregulation, but lacks detectable viral dissemination to dorsal root ganglia. We found that IFN-{gamma} expression was higher in CHIKV-infected joints, and direct IFN-{gamma} administration recapitulates mechanical hypersensitivity and neuronal stress independently of joint degeneration. Genetic or pharmacological disruption of IFN-{gamma} signalling prevented CHIKV-induced pain and neuronal stress without altering viral burden, demonstrating that IFN-{gamma} is required for both sensory dysfunction and joint pathology. By stratifying CHIKV-infected mice based on long-term nociceptive profiles, we show that persistent-pain subgroup characterized by elevated acute-phase systemic IFN-{gamma} and chronic peripheral neuropathic features. These findings were confirmed in human patients, where acute-phase IFN-{gamma} levels distinguished those who developed chronic arthralgia from those who recovered. Overall, our findings demonstrate that persistent post-CHIKV pain is driven by an IFN-{gamma}-mediated neuroimmune mechanism.

microbiology↗

bioRxiv2025

Leishmania amazonensis infection induces IL1β-dependent hyperalgesia, while dampening mechanical allodynia in C57BL/6 mice

Leishmaniases are neglected diseases causing significant deaths and disabilities. In Brazil, the most prevalent form is cutaneous leishmaniasis, characterized by painless lesions despite intense inflammation and ulceration. While BALB/c mice models exhibit hypersensitization to inflammatory stimuli, C57BL/6 mice better mimic human-like lesion progression and nociceptive responses. This study aimed to investigate the mechanisms underlying nociceptive changes in cutaneous leishmaniasis using the C57BL/6 model. Following infection with L. amazonensis, behavioral and nociceptive tests revealed unaltered mechanical nociception and motor capacity, though thermal hypersensitivity emerged during the chronic phase. Elevated IL-1{beta} production in the lesions and upregulation of TRPV1 in dorsal root ganglia (DRG) neurons were detected via ELISA and qPCR. Mice deficient in IL-1{beta}-related proteins or receptors exhibited higher thermal nociception thresholds, highlighting IL-1{beta}s role in heat hypersensitization during late infection stages. Microscopy of chronic lesions revealed tissue deformities, indicating desensitization to mechanical and inflammatory stimuli due to nerve terminal alterations and fibroplasia from regenerative processes. Conversely, thermal hypersensitivity in chronic phases was driven by IL-1{beta} effects on thermal nociceptive neurons in the DRG. These findings suggest that IL-1{beta} and TRPV1 contribute to thermal hypersensitivity, while structural changes in lesions underlie mechanical desensitization. This model provides insights into the complex nociceptive mechanisms of cutaneous leishmaniasis.

pathology↗

bioRxiv2022

SARS-CoV-2 spike protein induces long-term TLR4-mediated synapse and cognitive loss recapitulating Post-COVID syndrome

Cognitive dysfunction is often reported in post-COVID patients, but its underlying mechanisms remain unknown. While some evidence indicate that SARS-CoV-2 can reach and directly impact the brain, others suggest viral neuroinvasion as a rare event. Independently of brain viral infection, the ability of SARS-CoV-2 spike (S) protein to cross the BBB and reach memory-related brain regions has already been shown. Here, we demonstrate that brain infusion of S protein in mice induces late cognitive impairment and increases serum levels of neurofilament light chain (NFL), which recapitulates post-COVID features. Neuroinflammation, hippocampal microgliosis and synapse loss are induced by S protein. Increased engulfment of hippocampal presynaptic terminals late after S protein brain infusion were found to temporally correlate with cognitive deficit in mice. Blockage of TLR4 signaling prevented S-associated detrimental effects on synapse and memory loss. In a cohort of 86 patients recovered from mild COVID-19, genotype GG TLR4 -2604G>A (rs10759931) was associated with poor cognitive outcome. Collectively, these findings indicate that S protein directly impacts the brain and suggest that TLR4 is a potential target to prevent post-COVID cognitive dysfunction. One Sentence SummaryTLR4 mediates long-term cognitive impairment in mice and its genetic variant increases the risk of poor cognitive outcome in post-COVID patients.

neuroscience↗

bioRxiv2019

Association between uncontrolled eating and caudate responses to reward cues

Reward sensitivity has been hypothesized to play a significant role in a range of eating behaviors, including overeating. Previous functional magnetic resonance imaging (fMRI) findings in overweight individuals indicate heightened responses to food, but also to other reward types, suggesting generalized overactivity of the reward system. The current fMRI study investigated the relationship between general reward sensitivity and eating behavior in normal-weight individuals, while controlling for trait impulsivity. Participants were young adults, some demonstrating ADHD symptoms, allowing for a range of impulsivity profiles. A classical conditioning task was used to measure striatal responses to monetary reward stimuli. Uncontrolled eating scores from the Three Eating Factor Questionnaire were positively correlated with caudate responses to reward predicting cues. This association was not explained by self-reported impulsivity. The current findings provide support for heightened reward anticipation as a neural phenotype contributing to overeating.

neuroscience↗