Biology subjects

Sharma, L.

Publications and source records attributed to Sharma, L..

15 recordsLinked to original sources

bioRxiv2026

A Time-Resolved Single-Cell Atlas Reveals Infection-Status, Age-, and Sex-Dependent Immune Responses Drive Viral Disease Severity

The majority of mortality during viral infections occurs in older males; however, underlying mechanisms by which age and sex shape antiviral immunity and pathological inflammatory responses remain incompletely understood. Here, we performed time-resolved single-cell RNA sequencing across 16 conditions spanning age, sex, and four stages of influenza infection in mice, generating a high-resolution atlas. Aged mice demonstrate delayed antiviral and inflammatory responses in multiple myeloid cells, impairing viral clearance, which delays recovery. Similarly, endothelial cells from aging mice show prolonged inflammatory and antiviral gene signatures. Altered gene signatures in immune and endothelial cells result in a shift in endothelial-immune interactions in the aged lung. Further, the infection status of the cell is a major driver of transcriptional state, with infected myeloid cells exhibiting broad upregulation of genes, including interferon-stimulated, inflammatory, complement, and oxidative stress-related genes. To assess whether these age-associated transcriptional patterns are conserved in humans, we examined BAL cells obtained from healthy individuals and COVID-19 patients, and found that immune cells from aged COVID-19 patients had elevated antiviral and pro-inflammatory gene expression compared to cells from young patients. Our analyses of sex differences identified that multiple myeloid cell types in aged male mice, but not in young male mice, show persistent inflammatory responses at later stages of infection, a likely mechanism contributing to elevated mortality in older males. These data reveal how infection status of the cell, age, and sex interact to drive persistent inflammation and impaired resolution, providing a foundational resource for designing age- and sex-specific therapeutic strategies.

immunology↗

bioRxiv2026

Heme orchestrates a tissue stress response to proteolytic damage

Whereas cellular stress responses are well defined, tissue-level stress remains poorly understood. Proteases are among the most widespread enzymes, and excessive proteolytic activity drives diseases such as arthritis and chronic obstructive pulmonary disease, yet unifying features of this stress are unclear. Here, using the lung and diverse proteases, we identify a conserved injury signature of proteolytic stress marked by vascular disruption, red blood cell extravasation, and heme release that triggers oxidative stress. We show that alveolar macrophages act as primary sensors of this stress response, activating NRF2-dependent heme detoxification program and fibroblasts produce protease inhibitors to limit damage. Repeated exposure to proteolytic stress induces tissue adaptation and protects against subsequent injury and infection. These findings define a unifying framework for tissue-level proteolytic stress sensing and adaptation.

immunology↗

bioRxiv2024

Vascular endothelial growth factor-D improves lung vascular integrity during acute lung injury

Disorders in pulmonary vascular integrity are a prominent feature in many lung diseases. Paracrine signaling is highly enriched in the lung and plays a crucial role in regulating vascular homeostasis. However, the specific local cell-cell crosstalk signals that maintain pulmonary microvascular stability in adult animals and humans remain largely unexplored. In this study, we employed single-cell RNA-sequencing (scRNAseq)-based computational pipelines to systematically profile ligand-receptor (L/R) interactions within the lung microvascular niche and identified vascular endothelial growth factor-D (VEGF-D) as a key local factor with previously unrecognized barrier-protective properties in models of acute lung injury. Our scRNAseq data revealed that, under physiological conditions, soluble L/R interactions between mesenchymal cells, in particular alveolar fibroblast, and microvascular endothelial cells are predominantly associated with pathways involved in maintaining vascular integrity as compared to all other cells. Upon treatment with top identified ligands, we found that VEGF-D significantly enhanced endothelial barrier function and conferred protection against inflammatory challenges induced by tumor necrosis factor- (TNF-), interleukin-1{beta} (IL-1{beta}), and thrombin. This barrier-protective effect of VEGF-D was significantly attenuated by inhibition of VEGFR2, either through siRNA knockdown or pharmacological blockade using specific VEGFR2 inhibitors. Intravenous administration of recombinant VEGF-D in lipopolysaccharides (LPS)-induced acute lung injury models significantly reduced vascular permeability (7339 {+/-} 2510 (LPS) v.s. 5350 {+/-} 1821 (LPS + VEGF-D), p < 0.05), immune cell infiltration (0.791 {+/-} 0.199 x 106 WBC/mL (LPS) v.s. 0.540 {+/-} 0.190 x 106 WBC/mL (LPS + VEGF-D), p < 0.01), and the expression of pro-inflammatory markers TNF- and IL-6 in the lung tissue. This effect was abolished in VEGFR2iECKO mice, confirming that VEGF-D mediates its effects via VEGFR2-dependent signaling. This study demonstrates an unexpected protective role for VEGF-D in promoting lung endothelial barrier integrity and suggests that paracrine signaling from the alveolar fibroblast niche contributes critically to lung capillary homeostasis.

molecular biology↗

bioRxiv2024

Structural organization of p62 filaments and the cellular ultrastructure of calcium-rich p62-enwrapped lipid droplet cargo

The selective autophagy receptor p62/SQSTM1 (from hereon p62) is known to form higher-order filaments in vitro and to undergo liquid-liquid phase separation when mixed with poly-ubiquitin. We determined the full-length cryo-EM structure of p62 and elucidated a structured double helical filament scaffold composed of the PB1-domain associated with the flexible C-terminal part residing in the lumen and the solvent-accessible major groove. At different pH values and upon binding to soluble LC3, LC3-conjugated membranes and poly-ubiquitin, we observed p62 filament re-arrangements in the form of structural unwinding, disassembly, lateral association and bundling, respectively. In the cellular environment, under conditions of ATG5 knockdown leading to stalled autophagy, we imaged high-contrast layers consisting of p62 oligomers enwrapping lipid droplets by cryogenic electron tomography in cellulo, which we identified as calcium phosphate by compositional spectroscopy analysis. Together, we visualized the cellular ultrastructure of p62 oligomers with high calcium content as a potential intermediate step of autophagy initiation.

biophysics↗

bioRxiv2024

LncRNA TAAL is a Modulator of Tie1-Mediated Vascular Function in Diabetic Retinopathy

Diabetic retinopathy (DR), a leading cause of vision impairment and blindness, is characterized by abnormal retinal vascular changes due to chronic hyperglycemia. The Tie-1 signaling pathway, essential for vascular growth and remodeling, has emerged as a key therapeutic target, though its molecular mechanisms and interactome remain largely unclear. Through a protein-centric approach, we identified a novel lncRNA and named it Tie1-associated angiogenic lncRNA (TAAL). TAAL lncRNA regulates endothelial cell migration, proliferation, tube formation, and permeability by modulating ER-calcium homeostasis and cytoskeleton dynamics. In zebrafish, taal modulation led to angiogenic defects, which were rescued by human TAAL orthologue. Our molecular studies further revealed that TAAL negatively regulates Tie1 protein via ubiquitin-mediated degradation. Notably, TAAL expression is upregulated in the blood of DR patients and downregulated in endothelial DR cell models. Overexpression of TAAL restored endothelial permeability and VE-cadherin surface expression. These findings establish TAAL as a novel regulator of Tie1 protein turnover, with potential therapeutic implications for diabetic retinopathy.

genetics↗

bioRxiv2024

Epidermal Growth Factor Receptor Regulates Beclin-1 in Hyperoxia

While delivery of supplemental oxygen is a life-saving therapy, exposure to high levels of oxygen, called hyperoxia, is associated with increased mortality in the intensive care unit (ICU). Hyperoxia leads to oxidant-mediated acute lung injury (ALI) and pulmonary cell death, called hyperoxic acute lung injury (HALI). Elucidation of molecular mechanisms in HALI could identify therapeutic targets in ALI. In the current study, we examined in vivo effects of HALI on Beclin-1 (BCN1), a molecule that regulates autophagy and cell death. Effects of HALI on BCN1 and autophagy markers were examined in wildtype mice. Analysis of BCN1 and autophagy was completed via Western blot, RT-qPCR, and immunohistochemistry. In wildtype mice, HALI led to increased BCN1 in the lung and in the alveolar epithelium. HALI resulted in significant alterations in markers of autophagy in the lung, including reduced microtubule-associated protein 1B-light chain (LC3B)-II/-I ratios, suggesting reduced autophagic flux. HALI caused increased LDH release in human alveolar type-II cells derived from induced pluripotent stem cells (AT2siPSC), as well as reduced LC3B-II/-I ratios. We previously showed that inhibition of the tyrosine kinase receptor epidermal growth factor receptor (EGFR) is protective in HALI. EGFRWa5/+ mice, which have genetically reduced EGFR activity and improved survival in HALI, showed increased total BCN1, reduced phosphorylated-(p-)/total BCN1 ratios, and decreased LC3B-II/-I ratios in the lung in HALI compared with wildtype. Administration of wortmannin, a phosphatidylinositol-3 kinase (PI3K) inhibitor which decreases BCN1-mediated autophagy, led to increased mortality in HALI in wildtype mice. These data support that regulation of BCN1 and autophagy by EGFR is a protective mechanism in HALI, a pathway which warrants further study for its therapeutic potential. KEY MESSAGESHALI is associated with increased mortality in the ICU and causes alveolar epithelial cell death, but the role of BCN1 in HALI is not well defined. This study shows that BCN1, a molecule involved in autophagy and cell death, is regulated by EGFR in HALI in vivo. These results are significant because regulation by BCN1 and autophagy by EGFR is a novel pathway in HALI with therapeutic potential that warrants further study.

cell biology↗

bioRxiv2024

Damage sensing through TLR9 Promotes Viral Clearance and Recovery During Influenza Infection

Host response aimed at eliminating the infecting pathogen, as well as the pathogen itself, can cause tissue injury. Tissue injury leads to the release of a myriad of cellular components including mitochondrial DNA, which the host senses through pattern recognition receptors. How the sensing of tissue injury by the host shapes the anti-pathogen response remains poorly understood. In this study, we utilized mice that are deficient in toll-like receptor-9 (TLR9), which binds to unmethylated CpG DNA sequences such as those present in bacterial and mitochondrial DNA. To avoid direct pathogen sensing by TLR9, we utilized the influenza virus, which lacks ligands for TLR9, to determine how damage sensing by TLR9 contributes to anti-influenza immunity. Our data show that TLR9-mediated sensing of tissue damage promotes an inflammatory response during early infection, driven by the epithelial and myeloid cells. Along with the diminished inflammatory response, the absence of TLR9 led to impaired viral clearance manifested as a higher and prolonged influenza components in myeloid cells including monocytes and macrophages rendering them highly inflammatory. The persistent inflammation driven by infected myeloid cells led to persistent lung injury and impaired recovery in influenza-infected TLR9-/-mice. Further, we show elevated TLR9 activation in the plasma samples of patients with influenza and its association with the disease severity in hospitalized patients, demonstrating its clinical relevance. Overall, we demonstrate an essential role of damage sensing through TLR9 in promoting anti-influenza immunity and inflammatory response. Author SummaryTissue damage is an inevitable outcome of clinically relevant lung infections, but the host mechanisms for detecting such damage during infection are not well understood. We investigated the role of Toll-like receptor 9 (TLR9) in sensing tissue damage caused by influenza. Since influenza lacks TLR9 ligands, we hypothesized that TLR9 signaling is driven by tissue damage molecules like mitochondrial DNA (mtDNA). Our data indicate that TLR9 reduces early inflammatory lung injury but impairs viral clearance, resulting in extensive immune cell infection, persistent inflammation, and delayed recovery. Myeloid-specific TLR9 deletion ameliorated late-stage inflammatory responses. In humans, influenza-infected individuals exhibited elevated TLR9 activity and mtDNA levels in plasma compared to healthy controls, with higher TLR9 activation potential correlating with severe disease requiring ICU admission. These findings suggest that TLR9-mediated damage sensing triggers both inflammatory tissue injury and viral clearance. These data indicate that TLR9 activity can serve as a crucial biomarker and therapeutic target to limit influenza induced tissue injury.

immunology↗

bioRxiv2023

Sse1, Hsp110 chaperone of yeast, controls the cellular fate during Endoplasmic Reticulum-stress

Sse1 is a cytosolic Hsp110 molecular chaperone of yeast, Saccharomyces cerevisiae. Its multifaceted roles in cellular protein homeostasis as Nucleotide Exchange Factor (NEF), as protein-disaggregase and as a Chaperone linked to Protein Synthesis (CLIPS), are well documented. In the currently study, we show that SSE1 genetically interacts with IRE1 and HAC1, the Endoplasmic Reticulum-Unfolded Protein Response (ER-UPR) sensors implicating its role in ER protein homeostasis. Interestingly, absence of this chaperone imparts unusual resistance to tunicamycin-induced ER stress which depends on the intact Ire1-Hac1 mediated ER-UPR signalling. Furthermore, cells lacking SSE1 show ER-stress-responsive inefficient reorganization of translating ribosomes from polysomes to monosomes and increased monosome content that drive uninterrupted protein translation. In consequence, the kinetics of ER-UPR is starkly different in sse1{Delta} strain where we show that stress response induction and restoration of homeostasis is prominently faster in contrast to the wildtype (WT) cells. Importantly, Sse1 plays a critical role in controlling the ER-stress mediated cell division arrest which is escaped in sse1{Delta} strain during chronic tunicamycin stress. Consequently, sse1{Delta} strain shows significantly higher cell viability in comparison to WT yeast, following short-term as well as long-term tunicamycin stress. In summary, we demonstrate a new role of Sse1 in ER protein homeostasis where the chaperone genetically interacts with ER-UPR pathway, controls the protein translation during ER stress and the kinetics of ER-UPR. More importantly, we show the crtical role of Sse1 in regulating the ER-stress-induced cell division arrest and cell death during global ER stress by tunicamycin. Author SummarySse1 is a cytosolic Hsp110 molecular chaperone of yeast, Saccharomyces cerevisiae. It performs various functions as Nucleotide Exchange Factor (NEF), as a protein-disaggregase and as a Chaperone linked to Protein Synthesis (CLIPS) to maintain a healthy proteome in the cytosol. In the present study, we show that SSE1 is a critical player to maintain Endoplasmic Reticulum (ER) protein homeostasis. We report that SSE1 genetically interacts with the ER-Unfolded Protein Response (ER-UPR) sensors, IRE1 and HAC1. In absence of SSE1, yeast cells gain unusual fitness to tunicamycin (Tm)-induced ER stress which depends on the functional Ire1-Hac1 mediated ER-UPR signalling. Furthermore, Sse1 controls the ribosomal organization during tunicamycin-induced ER-stress and in absence of the chaperone the amount of polysomes and monosmes are high leading to uninterrupted protein translation during ER stress. Consequently, sse1{Delta} strain exhibits starkly different ER-UPR kinetics compared to wildtype (WT) cells. Importantly, our data reveal that cell division arrest and cell death due to Tm-induced ER-stress is critically controlled by Sse1.

cell biology↗

bioRxiv2022

A novel fluorobenzothiazole RBx 10080758 as a dual inhibitor against bacterial GyraseB (GyrB) and Topoisomerase IV (parE) of Gram-positive pathogens causing skin and respiratory infections

Development of a novel inhibitor targeting Gyrase B and Topoisomerase IV offers a potential opportunity to combat the drug resistance. In the present study, we extensively investigated the efficacy of RBx 10080758, a novel fluorobenzothiazole, against skin and respiratory infections caused by Staphylococci and Streptococci in in vitro and in vivo models. RBx 10080758 showed a potent IC50 of 0.06 M against Gyrase and Topoisomerase IV and also exhibited a strong whole cell in vitro activity with MIC ranges of 0.015-0.06, 0.015-0.03, 0.008-0.03, 0.008-0.03, 0.008-0.0.06, 0.015-0.06 g/ml against Staphylococcus. aureus, Streptococcus pneumoniae, Coagulase negative Staphylococci, Streptococcus viridans, Streptococcus pyogenes and Enterococcus, respectively. As expected from the novel class of molecule, it retains potent even against linezolid and vancomycin resistant strains. Interesting, in mouse systemic infection 10 mg/kg, IV dose protected 100% mice from lethal infections. In rat thigh infection model with MRSA WCUH29 at 45 mg/kg exhibited >3-log10 cfu reduction in thigh muscles. RBx 10080758 displayed potent in vitro and in vivo activity against a panel of MDR Gram-positive bacteria. As a novel chemical class, the fluorobenzothiazoles have the potential to become clinically viable antibiotics, to address the drug resistance problem by its unique dual targeting mechanism of action.

microbiology↗

bioRxiv2021

Actin filaments act as a size-dependent diffusion barrier around centrosomes

The centrosome, a non-membranous organelle, constrains various soluble molecules locally to execute its functions. As the centrosome is surrounded by various dense components, we hypothesized that the centrosome may be bordered by a putative diffusion barrier. After quantitatively measuring the trapping kinetics of soluble proteins of varying size at centrosomes by a chemically inducible diffusion trapping assay, we found that centrosomes were highly accessible to soluble molecules with a Stokes radius of [≤] 5.1 nm, whereas larger molecules rarely reach centrosomes, indicating the existence of a size-dependent diffusion barrier at centrosomes. The permeability of barriers was tightly regulated by branched actin filaments outside of centrosomes. Such barrier gated the microtubule nucleation. We propose that actin filaments spatiotemporally constrain the distribution of molecules at centrosomes in a size-dependent manner. Significance StatementCentrosome maintains its microenvironment without membrane. Whether the dense protein complexes outside centrosomes including pericentriolar matrix, microtubules, and branched actin filaments provide physical obstruction is unclear yet. We here established a series of new tools for quantitative evaluation of the diffusion rates of varisized soluble proteins in different sub-compartments of centrosomes. Our results demonstrated that branched actin filaments, but not pericentriolar matrix or microtubules, around centrosome have acted as a size-dependent diffusion barrier and physically constrain centrosome microtubule nucleation.

cell biology↗

bioRxiv2020

Type I Interferon Limits Viral Dissemination-Driven Clinical Heterogeneity in a Native Murine Betacoronavirus Model of COVID-19

Emerging clinical data demonstrates that COVID-19, the disease caused by SARS-CoV2, is a syndrome that variably affects nearly every organ system. Indeed, the clinical heterogeneity of COVID-19 ranges from relatively asymptomatic to severe disease with death resultant from multiple constellations of organ failures. In addition to genetics and host characteristics, it is likely that viral dissemination is a key determinant of disease manifestation. Given the complexity of disease expression, one major limitation in current animal models is the ability to capture this clinical heterogeneity due to technical limitations related to murinizing SARS-CoV2 or humanizing mice to render susceptible to infection. Here we describe a murine model of COVID-19 using respiratory infection with the native mouse betacoronavirus MHV-A59. We find that whereas high viral inoculums uniformly led to hypoxemic respiratory failure and death, lethal dose 50% (LD50) inoculums led to a recapitulation of most hallmark clinical features of COVID-19, including lymphocytopenias, heart and liver damage, and autonomic dysfunction. We find that extrapulmonary manifestations are due to viral metastasis and identify a critical role for type-I but not type-III interferons in preventing systemic viral dissemination. Early, but not late treatment with intrapulmonary type-I interferon, as well as convalescent serum, provided significant protection from lethality by limiting viral dissemination. We thus establish a Biosafety Level II model that may be a useful addition to the current pre-clinical animal models of COVID-19 for understanding disease pathogenesis and facilitating therapeutic development for human translation.

immunology↗

bioRxiv2020

Identification of potent and safe antiviral therapeutic candidates against SARS-CoV-2

COVID-19 pandemic has infected millions of people with mortality exceeding 300,000. There is an urgent need to find therapeutic agents that can help clear the virus to prevent the severe disease and death. Identifying effective and safer drugs can provide with more options to treat the COVID-19 infections either alone or in combination. Here we performed a high throughput screen of approximately 1700 US FDA approved compounds to identify novel therapeutic agents that can effectively inhibit replication of coronaviruses including SARS-CoV-2. Our two-step screen first used a human coronavirus strain OC43 to identify compounds with anti-coronaviral activities. The effective compounds were then screened for their effectiveness in inhibiting SARS-CoV-2. These screens have identified 24 anti-SARS-CoV-2 drugs including previously reported compounds such as hydroxychloroquine, amlodipine, arbidol hydrochloride, tilorone 2HCl, dronedarone hydrochloride, and merfloquine hydrochloride. Five of the newly identified drugs had a safety index (cytotoxic/effective concentration) of >600, indicating wide therapeutic window compared to hydroxychloroquine which had safety index of 22 in similar experiments. Mechanistically, five of the effective compounds were found to block SARS-CoV-2 S protein-mediated cell fusion. These FDA approved compounds can provide much needed therapeutic options that we urgently need in the midst of the pandemic.Competing Interest StatementThe authors have declared no competing interest.View Full Text

microbiology↗

bioRxiv2019

Worldwide recombination in emergent white-nose syndrome pathogen Pseudogymnoascus destructans

Pseudogymnoascus destructans (Pd), the emergent fungus causing bat "White-Nose Syndrome", responsible for [~]6 million mortalities in the United States (US), is thought to expand clonally in North America and Europe. Presence of distinct mating-types in Europe led to numerous research attempts searching for population sexuality worldwide. This study not only presents the first evidence of genetic recombination in Pd but also detects recombination in Pd genotype data generated by previous studies in Europe and North America, through clone-corrected linkage disequilibrium analysis. Portuguese and other European populations are apparently reproducing through sex between two mating-types. Seeming parasexual recombination in the invasive single mating-type US population rings alarms for the North American bat populations and deserves urgent attention. This study emphasizes on clone-correction in linkage disequilibrium analysis. One Sentence SummaryClone-correction yielded signs of elusive recombination in the global "clonal" populations of white-nose syndrome pathogen.

ecology↗

bioRxiv2019

A Maxent modelling with a geospatial approach for the Habitat suitability of Flamingos in an Evanescing Ramsar site (Sambhar Lake, India) over the changing climatic scenarios

Wetlands play a crucial role in the biosphere and provide numerous services. They performed multiple functions such as groundwater recharge, water purification, conservation of biological resources, act as a carbon sink and habitat of amphibians and birds. A Ramsar site-the Sambhar Lake is one of the largest inland saline wetland present in the arid region of Rajasthan, India has unique habitat suitability for the winter avifauna migrants like flamingoes and falcons. The occurrence of suitable climatic conditions and food availability like brine shrimps (Artemia salina) attracts flocks of migratory birds. From the last three decades, Sambhar Lake has been continuously facing degradation due to anthropogenic activities, which disturb Lakes natural ecology and existence. These cause disturbances in habitat suitability of migratory birds in the Sambhar Lake, which leads to a reduction of population density of migratory birds. Therefore, this study aimed to assess the degradation and vulnerability of Sambhar Lake and the habitat suitability of migratory birds using Maxent Habitat Suitability model. This model provides a platform to integrate the birds occurrence data with the bioclimatic variables using remote sensing and Geographical Information System, and provides birds habitat suitability as well as predicts future birds occurrence scenarios. Landsat-5 and Sentinel-2 imagery for the year 1996 and 2019 respectively were used in this study. Four indicators such as LULC NDWI, MSI and SABI depicts the environmental condition of the Sambhar Lake. Output form Maxent model reveals that the Sambhar lake area with increasing anthropogenic activities has become unsuitable for flamingos. A remarkable loss of breeding sites of animal, particularly avian fauna (flamingos) is seen in the recent years due to different types of threats posed on the Ramsar site. Increase in Salt crust and Vegetation area from 36.8055 to 123.837 Sq. Km. and 26.5347 to 36.857 Sq. Km. respectively have taken place. While a decrease in saline water area from 88.8309 to 19.3256 Sq. Km has been observed, within the vicinity of Sambhar Lake as clearly shown through LULC map. The future prediction of the distribution of species in the region for the year 2050 shows that the most suitable regions will be near to Jhapok and nearby waters of Salt Lake City as the drains from the city opens in the lake where the flamingoes get Algae in the form of food. Active steps are needed for the lake conservation to reduce the risks of migratory birds population.

ecology↗

bioRxiv2018

The fungal ligand chitin directly binds and signals inflammation dependent on oligomer size and TLR2

Chitin is a highly abundant polysaccharide and linked to fungal infection and asthma. Unfortunately, its polymeric structure has hampered the identification of immune receptors directly binding chitin and signaling immune activation and inflammation, because purity, molecular structure and molarity are not well definable for a polymer typically extracted from biomass. Therefore, by using defined chitin (N-acetyl-glucosamine) oligomers, we identified six subunit long chitin chains as the smallest immunologically active motif and the innate immune receptor Toll-like receptor (TLR) 2 as the primary fungal chitin receptor on human and murine immune cells. Chitin oligomers directly bound TLR2 with nanomolar affinity and showed both overlapping and distinct signaling outcomes compared to known mycobacterial TLR2 ligands. Conversely, chitin oligomers shorter than 6 subunits were inactive or showed antagonistic effects on chitin/TLR2-mediated signaling, hinting to a size-dependent sensing/activation system unexpectedly conserved in plants and humans. Since blocking the chitin-TLR2 interaction effectively prevented chitin-mediated inflammation in vitro and in vivo, our study highlights the chitin TLR2 interaction as a potential target for developing novel therapies in chitin-related pathologies and fungal disease.

immunology↗