Biology subjects

Khan, N.

Publications and source records attributed to Khan, N..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Phytochemical Analysis and Nematicidal Activity of Medicinal Plants Against Meloidogyne javanica

This study examined the nematicidal potential of ethanol extracts derived from four plants, namely Actinidia deliciosa (Chev.), Carica papaya, Citrus paradise, and Raphanus sativus, against the root-knot nematode Meloidogyne javanica. Experimental results indicated a significant reduction in the survival of second-stage juveniles of M. javanica when exposed to these plant extracts. Notably, concentrations of 2% and 1% were found to be more effective in comparison to 0.5% and 0.25%, yielding statistically significant outcomes. Furthermore, the mortality rate of the nematodes exhibited a direct correlation with the duration of exposure for most plant extracts. The fruit extracts obtained from A. deliciosa, C. papaya, C. paradise, and R. sativus demonstrated a substantial decrease in nematode infestation compared to the control group. The nematicidal activity of KI3a (BuOH) significant from 0.1356 to 1.9076 over 72 hours, while P-KI-2a (EtOAc) showed rose from 0.1206 to 0.6456. In compare, GF-3 (EtOAc) and Carbofuran to 0.0179 and 0.0098, respectively. PA-1 (MeOH) and RS-3 (EtOAc) showed modest nematicidal potential. This research emphasizes the efficacy of plant extract in mitigating root-knot nematode infestation, offering a promising alternative to chemical managements. Additionally, comprehensive phytochemical analysis should be achieved to recognize the active chemical constituents responsible for their effects. Exploring synergistic effects between these compounds and other natural or synthetic agents could further improve their potential applications in sustainable agriculture, improving crop protection and promoting eco-friendly practices.

plant biology↗

bioRxiv2024

β-Glucan Reprograms Neutrophils to Induce Disease Tolerance Against Influenza A Virus

ABSTRACTDisease tolerance is an evolutionarily conserved host defence strategy that preserves tissue integrity and physiology without affecting pathogen load. Unlike host resistance, the mechanisms underlying disease tolerance remain poorly understood. In the present study, we investigated whether an adjuvant ({beta}-glucan) can reprogram innate immunity to provide protection against Influenza A virus (IAV) infection. Here we observe that {beta}-glucan treatment reduced the morbidity and mortality against IAV infection, independent of host resistance (viral load). Increased survival of {beta}-glucan treated mice against IAV is associated with the accumulation of neutrophils via RoR{gamma}t+ T cells in the lung tissue. Using gain-and-loss-of-function approaches, we demonstrate that {beta}- glucan reprogrammed neutrophils are essential for promoting disease tolerance, limiting pulmonary tissue damage, and enhancing survival against IAV infection. {beta}-glucan treatment promotes granulopoiesis in a type 1 interferon-dependent manner that leads to the generation of a unique subset of neutrophils, which are less mature with higher mitochondrial mass utilizing mitochondrial oxidative (OXPHOS) metabolism. Collectively, our data indicate that {beta}-glucan reprograms hematopoietic stem cells (HSCs) to generate neutrophils with a novel "regulatory" function, which is required for promoting disease tolerance and maintaining lung tissue integrity against viral infection.

immunology↗

bioRxiv2024

The ventral hippocampal-nucleus accumbens shell circuit drives approach decisions under social novelty and learned cue approach-avoidance conflict

Successful resolution of approach-avoidance conflict (AAC) is fundamentally important for survival, and its dysregulation is a hallmark of many neuropsychiatric disorders, and yet the underlying neural circuit mechanisms are not well elucidated. Converging human and animal research has implicated the anterior/ventral hippocampus (vHPC) as a key node in arbitrating AAC in a region-specific manner. In this study, we sought to target the vHPC CA1 projection pathway to the nucleus accumbens (NAc) to delineate its contribution to AAC decision-making, particularly in the arbitration of learned reward- and punishment signals, as well as innate signals. To this end, we used pathway-specific chemogenetics in male and female Long Evans rats to inhibit the NAc shell projecting vHPC CA1 neurons while rats underwent a test in which cues of positive and negative valence were presented concurrently to elicit AAC. Further behavioral assays of social preference and memory, reward and punishment cue processing, anxiety, and novelty processing were administered to further interrogate the conditions under which the vCA1-NAc shell pathway is recruited. Chemogenetic inhibition of the vCA1-NAc shell circuit resulted in animals exhibiting increased decision-making time and avoidance bias specifically in the face of motivational conflict, as the same behavioral phenotype was absent in separate conditioned cue preference and avoidance tests. vCA1-NAc shell inhibition also led to a reduction in seeking social interaction with a novel rat but did not alter anxiety-like behaviors. The vCA1-NAc shell circuit is therefore critically engaged in biasing decisions to approach in the face of social novelty and approach-avoidance conflict. Dysregulation of this circuit could lead to the precipitation of addictive behaviours in substance abuse, or potentiation of avoidance in situations of approach-avoidance conflict.

neuroscience↗

bioRxiv2024

The effect of a dominant kinase-dead Csf1r mutation associated with adult-onset leukoencephalopathy on brain development and neuropathology.

Amino acid substitutions in the kinase domain of the human CSF1R protein are associated with autosomal dominant adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). To model the human disease, we created a disease-associated mutation (Glu631Lys; E631K) in the mouse Csf1r locus. Previous analysis demonstrated that heterozygous mutation (Csf1rE631K/+) had a dominant inhibitory effect on CSF1R signaling in vitro and in vivo but did not recapitulate the pathology of the human disease. We speculated that leukoencephalopathy in humans requires an environmental trigger and/or epistatic interaction with common neurodegenerative disease-associated alleles. Here we examine the impact of heterozygous Csf1r mutation on microglial phenotype, normal postnatal brain development, age-related changes in gene expression and on two distinct pathologies in which microgliosis is a prominent feature, prion disease and experimental autoimmune encephalitis (EAE). The heterozygous Csf1rE631K/+ mutation reduced microglial abundance and the expression of microglial-associated transcripts relative to wild-type controls at 12 weeks and 43 weeks of age but had no selective effect on homeostatic markers such as P2ry12. An epistatic interaction was demonstrated between Csf1rE631K/+ and Cxc3r1EGFP/+ genotypes leading to dysregulated microglial and neuronal gene expression in both hippocampus and striatum. Heterozygous Csf1rE631K mutation reduced the microgliosis associated with both diseases. There was no significant impact on disease severity or progression in prion disease. In EAE, induced expression of inflammation-associated transcripts in the hippocampus and striatum was suppressed in parallel with microglia-specific transcripts, but spinal cord demyelination was exacerbated. The results support a dominant-negative model of CSF1R-associated leukoencephalopathy and likely contributions of an environmental trigger and/or genetic background to neuropathology.

neuroscience↗

bioRxiv2024

Stem rot affects the structure of rhizosphere microbiome in Berseem Clover (Trifolium alexandrinum)

Rhizosphere microbiome plays an essential role in maintaining plant health and productivity. Fungal and bacterial diseases may affect the rhizosphere-associated microbial communities and overall structure of plant microbiome. Here, we studied the effect of stem rot of berseem clover on the bacterial and fungal communities associated with the rhizosphere. We analyzed the rhizosphere-associated bacterial and fungal microbiome from healthy and infected berseem clover collected from three sampling sites by using 16S rRNA and ITS based Illumina sequencing metabarcoding approach. Microbiome analysis showed that healthy plants had higher bacterial and fungal diversity as compared to stem rot infected plants. At the genus level, bacterial genera Rhizobium and Comamonas were more abundant in healthy plants while Pantoea was more abundant in infected plants and fungal genera Sclerotinia, Fusarium and Cladorrhinum were more abundant in infected plants while Microdochium and Cladosporium were distinctively abundant in healthy Berseem. Functional characterization of bacterial and fungal microbiomes revealed that bacterial communities from infected plants showed more abundance of bacteria with functions replication and repair, enzyme families and biosynthesis of other secondary metabolites as compared to healthy plant microbiome and decreased in fungal groups including arbuscular mycorrhiza and soil saprotrophs and an increase in plant saprotrophs and fungal parasite-plant pathogens. This study provides comprehensive information about the structure and composition of bacterial and fungal communities associated with the berseem clover rhizosphere that could be utilized for future research on the control of stem rot of berseem clover.

plant biology↗

bioRxiv2024

Formulation, Characterization and Pharmacokinetic Evaluation of Amorphous Solid Dispersions of Glibenclamide for Bioavailability Enhancement in Wistar Rats

Oral bioavailability of Glibenclamide (Glb) was appreciably improved by forming amorphous solid dispersion (ASD) with Poloxamer-188 (P-188). Poloxamer-188 substantially enhanced the solubility and thereby dissolution rate of the BCS Class-II drug, Glibenclamide (Glb) and simultaneously exhibited better stabilizing effect of amorphous solid dispersion prepared by solvent evaporation method. The physical state of the dispersed Glibenclamide in the polymeric matrix was characterized by differential scanning calorimetry, X-ray diffraction, scanning electron microscope and Fourier Transform Infrared studies. In vitro drug release in buffer (pH 7.2) revealed that amorphous solid dispersion at the Glb-P-188 ratio of 1:6 (SDE4) improved the dissolution of Glibenclamide 90% within 3 hrs. Pharmacokinetic study of the solid dispersion formulation (SDE4) formulation in wistar rats showed that oral bioavailability of the drug was greatly increased as compared to market tablet formulation, Daonil(R). Solid dispersion formulation (SDE4) resulted in approximately two fold higher AUC0-24 hrs. Solid dispersion formulation (SDE4) formulation was found stable during the study period of six months.

biochemistry↗

bioRxiv2024

Artemisinin-resistant Plasmodium falciparum Kelch13 mutant proteins display reduced heme-binding affinity and decreased artemisinin activation

The rapid emergence of artemisinin resistance (ART-R) poses a challenge to global malaria control efforts. ART potency is triggered by ferrous iron- and/or heme-mediated cleavage of the endoperoxide bond to generate reactive heme-ART alkoxy radicals and covalent heme-ART adducts that alkylate parasite targets or inhibit the detoxification of heme into {beta}-hematin crystals; both of which lead to parasite death. Mutations in the P. falciparum Kelch-containing protein Kelch13 (PfKekch13) confer clinical ART-R, in which the resistant parasites exhibit impaired hemoglobin uptake, reduced heme yield, and thus decreased ART activation. However, a more direct involvement of PfKelch13 in heme-mediated ART activation has not been reported. Here, we show that recombinant, purified PfKelch13 wild-type (WT) protein displays measurable binding affinity for both iron and heme, the main effectors for ART activation. Comparative biochemical analyses further indicate weaker heme-binding affinities in the two Southeast Asian ART-R PfKelch13 mutants C580Y and R539T compared to the ART-sensitive WT and A578S mutant proteins, which ultimately translates into reduced yield of heme-ART derivatives. In conclusion, this study provides the first evidence for regulated ART activation via the heme-binding propensity of PfKelch13, which may contribute towards modulating the level of ART-R in malaria parasites with PfKelch13 mutations.

biochemistry↗

bioRxiv2023

Vaginal Lactobacillus fatty acid response mechanisms reveal a novel strategy for bacterial vaginosis treatment

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related species, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the human vaginal microbiota and sequesters OA in a derivative form that only ohyA-harboring organisms can exploit. Finally, OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro model of BV, suggesting a novel approach for treatment.

microbiology↗

bioRxiv2023

NMR structure of the Orf63 pro-lytic protein from lambda bacteriophage

The orf63 gene resides in a region of the lambda bacteriophage genome between the exo and xis genes and is among the earliest genes transcribed during infection. In lambda phage and Shiga toxin (Stx) producing phages found in enterohemorrhagic E. coli (EHEC) associated with food poisoning, Orf63 expression reduces the host survival and hastens the period between infection and lysis thereby giving it pro-lysogenic qualities. The NMR structure of dimeric Orf63 reveals a fold consisting of two helices and one strand that all make extensive intermolecular contacts. Structure-based data mining failed to identify any Orf63 homolog beyond the family of temperate bacteriophages. A machine learning approach was used to design an amphipathic helical ligand that bound a hydrophobic cleft on Orf63. This approach may open a new path towards designing therapeutics that antagonize the contributions of Stx phages in EHEC outbreaks.

biochemistry↗

bioRxiv2023

Enhancing farmed striped catfish (Pangasianodon hypophthalmus) robustness using dietary β-glucan

{beta}-glucan is a well-documented feed additive for its potent immunostimulatory properties in many farmed fish species. This study examined how it can also be a promising growth promoter, modulate antioxidant enzyme activities, and act as an anti-stress agent in striped catfish (Pangasianodon hypophthalmus). A 12-week feeding experiment was untaken to determine the effects of dietary {beta}-glucan supplementation at graded levels (0, 0.5, 1.0, and 1.5 g kg-1). Measured indicators suggest that a dietary inclusion level of 1.5 g kg-1 {beta}-glucan gave the highest positive responses: weight gain (120.10 g fish-1), survival (98.30 %), and lower FCR (1.70) (P<0.05). Whole body proximate analysis had only revealed that crude protein was significantly affected by the dietary inclusion of {beta}-glucan (P<0.05), with the highest protein content (19.70 %) being in fish that were fed with 1.5 g kg-1 {beta}-glucan. Although other inclusion levels (i.e., 0.5 and 1 g kg-1) of {beta}-glucan did not enhance body protein content (P>0.05). The assessment of fatty acid composition in muscle, liver, and adipose tissues showed modifications with the inclusion of {beta}-glucan. Antioxidative-related enzyme activities (inc. catalase, glutathione peroxidase, and superoxide dismutase) that were measured in the liver had higher levels when fed with {beta}-glucan inclusion diets (P<0.05). Following the feed trial, fish were subjected to crowding stress treatment. It was subsequently found that catfish fed with {beta}-glucan-based diet groups had lower levels of blood stress-related indicators compared to the control group with no dietary {beta}-glucan. The use of 1.5 g kg-1 of dietary {beta}-glucan resulted in the lowest measured levels of cortisol (43.13 ng mL-1) and glucose (50.16 mg dL-1). This study has demonstrated that the dietary inclusion of {beta}-glucan can have functional benefits beyond the immunological enhancements in striped catfish. Furthermore, its use can increase production levels and mitigate the stress associated with intensive farming practices.

zoology↗

bioRxiv2023

Linoleic acid supplementation reverses microglial response to diet induced-obesity at hypothalamic, cortical and subcortical level in mice

Obesity is a major risk factor for neuropsychiatric alterations. Fatty regimes lead to systemic and cerebral inflammation, the latest acting through lipotoxicity on hypothalamic structures controlling energy homeostasis. Since literature points to a protective effect of linoleic acid (LA) on mood disorders through the regulation of systemic inflammation, we investigated how five weeks of LA supplementation modulates emotional behaviour and microglia-related neuroinflammation. C57BL/6j mice were fed with either a high-fat (HFD) or a standard diet for 12 weeks, underwent a battery of behavioural tests and were subsequently sacrificed for immunofluorescence staining targeting microglia-specific calcium-binding proteins (IBA-1). Neuroinflammation severity was approximated in multiple hypothalamic, cortical and subcortical regions. Our results show an anxio-depressive-like effect of sustained HFD that neither was alleviated nor worsen with LA supplementation. Increased IBA-1 expression in the HFD group was substantially reversed with LA supplementation. Thus, our results suggest anti-neuroinflammatory properties of LA not restricted to hypothalamic areas, but also evident at the cortical and subcortical level. This study is therefore relevant in the frame of obesity and neuropsychiatric disorders with a neuroinflammatory basis. Further investigation may provide more information to justify dietary strategies aiming at reducing the impact of obesity associated comorbidities.

neuroscience↗

bioRxiv2023

Leukemic stem cells hijack lineage inappropriate signalling pathways to promote their growth

Acute Myeloid Leukemia (AML) is caused by multiple mutations which dysregulate growth and differentiation of myeloid cells. Cells adopt different gene regulatory networks specific to individual mutations, maintaining a rapidly proliferating blast cell population with fatal consequences for the patient if not treated. The most common treatment option is still chemotherapy which targets such cells. However, patients harbour a population of quiescent leukemic stem cells (LSCs) which can emerge from quiescence to trigger relapse after therapy. The processes that allow such cells to re- grow remain unknown. Here, we examined the well characterised t(8;21) AML sub-type as a model to address this question. Using a novel t(8;21) patient-derived xenograft model, we show that t(8;21) LSCs aberrantly activate the VEGF and IL-5 signalling pathways. Both pathways operate within a regulatory circuit consisting of the driver oncoprotein RUNX1::ETO and an AP-1/GATA2 axis allowing LSCs to re-enter the cell cycle while preserving self-renewal capacity.

cancer biology↗

bioRxiv2022

Role of spike in the pathogenic and antigenic behavior of SARS-CoV-2 BA.1Omicron

The recently identified, globally predominant SARS-CoV-2 Omicron variant (BA.1) is highly transmissible, even in fully vaccinated individuals, and causes attenuated disease compared with other major viral variants recognized to date1-7. The Omicron spike (S) protein, with an unusually large number of mutations, is considered the major driver of these phenotypes3,8. We generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron in the backbone of an ancestral SARS-CoV-2 isolate and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escapes vaccine-induced humoral immunity, mainly due to mutations in the receptor-binding motif (RBM), yet unlike naturally occurring Omicron, efficiently replicates in cell lines and primary-like distal lung cells. In K18-hACE2 mice, while Omicron causes mild, non-fatal infection, the Omicron S-carrying virus inflicts severe disease with a mortality rate of 80%. This indicates that while the vaccine escape of Omicron is defined by mutations in S, major determinants of viral pathogenicity reside outside of S.

microbiology↗

bioRxiv2022

Mycelial nutrient transfer promotes bacterial co-metabolic organochlorine pesticide degradation in nutrient-deprived environments.

Biotransformation of soil organochlorine pesticides (OCP) is often impeded by a lack of nutrients relevant for bacterial growth and/or co-metabolic OCP biotransformation. By providing space-filling mycelia, fungi promote contaminant biodegradation by facilitating bacterial dispersal and the mobilization and release of nutrients in the mycosphere. We here tested whether mycelial nutrient transfer from nutrient-rich to nutrient-deprived areas facilitates bacterial OCP degradation in a nutrient-deficient habitat. The legacy pesticide hexachlorocyclohexane (HCH), a non-HCH-degrading fungus (Fusarium equiseti K3) and a co-metabolically HCH-degrading bacterium (Sphingomonas sp. S8) isolated from the same HCH-contaminated soil were used in spatially structured model ecosystems. Using 13C-labelled fungal biomass and protein-based stable isotope probing (protein-SIP), we traced the incorporation of 13C fungal metabolites into bacterial proteins while simultaneously determining the biotransformation of the HCH isomers. The relative isotope abundance (RIA, 7.1 - 14.2%), labeling ratio (LR, 0.13 - 0.35), and the shape of isotopic mass distribution profiles of bacterial peptides indicated the transfer of 13C-labeled fungal metabolites into bacterial proteins. Distinct 13C incorporation into the haloalkane dehalogenase (linB) and 2,5-dichloro-2,5-cyclohexadiene-1,4-diol dehydrogenase (LinC), as key enzymes in metabolic HCH degradation, underpin the role of mycelial nutrient transport and fungal-bacterial interactions for co-metabolic bacterial HCH degradation in heterogeneous habitats. Nutrient uptake from mycelia increased HCH removal by twofold as compared to bacterial monocultures. Fungal-bacterial interactions hence may play an important role in the co-metabolic biotransformation of OCP or recalcitrant micropollutants (MPs).

microbiology↗

bioRxiv2022

A neural mechanism of cognitive reserve: The case of bilingualism

Cognitive Reserve (CR) refers to the preservation of cognitive function in the face of age-or disease-related neuroanatomical decline. While bilingualism is known to contribute to CR, the extent to which, and what particular aspect of, second language experience contributes to CR are debated, and the underlying neural mechanism(s) unknown. Intrinsic functional connectivity reflects experience-dependent neuroplasticity that occurs across timescales ranging from minutes to decades, and may be a neural mechanism underlying CR. To test this hypothesis, we used voxel-based morphometry and resting-state functional connectivity analyses of MRI data to compare structural and functional brain integrity between bilingual and monolingual older adults, matched on cognitive performance using a rigorous propensity score matching technique, and across levels of second language proficiency measured as a continuous variable. Bilingualism, and degree of second language proficiency in particular, were associated with lower grey matter integrity in a hub of the default mode network - a region that is particularly vulnerable to decline in aging and dementia - but preserved functional network organization that resembled the young adult brain. Our findings confirm that lifelong bilingualism contributes to CR through experience-dependent maintenance of optimal functional network structure of the domain-general attentional control network across the lifespan.

neuroscience↗

bioRxiv2022

High resolution photocatalytic mapping of SARS-CoV-2 Spike protein-host cell membrane interactions

Identifying protein environments at the virus-host cell interface can improve our understanding of viral entry and pathogenesis. SARS-CoV-2, the virus behind the ongoing COVID-19 pandemic, uses the cell surface ACE2 protein as a major receptor, but the contribution of other cellular proteins in the entry process is unknown. To probe the microenvironment of SARS-CoV-2 Spike-ACE2 protein interactomes on human cells, we developed a photocatalyst-based viral-host protein microenvironment mapping platform (ViraMap) employing iridium photocatalysts conjugated to Spike for visible-light driven proximity labelling on host cells. Application of ViraMap on ACE2-expressing cells captured ACE2, the established co-receptor NRP1, as well as other proteins implicated in host cell entry and immunomodulation. We further investigated these enriched proteins via loss-of-function and over-expression in pseudotype and authentic infection models and observed that the Ig receptor PTGFRN and tyrosine kinase ligand EFNB1 can serve as SARS-CoV-2 entry factors. Our results highlight additional host targets that participate infection and showcase ViraMap for interrogating virus-host cell surface interactomes.

biochemistry↗

bioRxiv2022

Mitochondrial TFAM in the Regulation of FOXP3+ T cell Mediated Maintenance of CD4+ T Cell Landscapes

Foxp3 regulatory T cells (Tregs) maintain immune homeostasis, yet the process that preserves their stability during aging remain unclear. Mechanistic progress has been hindered by models that ablate Tregs or delete Foxp3, which induce acute autoimmunity and prevent longitudinal study of physiological regulatory drift. Here, we establish a dose-dependent mitochondrial framework that preserves Treg lineage survival while permitting gradual metabolic attenuation. Using Treg-restricted TFAM modulation, a complementary haploinsufficient model, and whole-spleen single-cell profiling. We identify lineage-selective immune remodeling characterized by contraction of naive CD8 and follicular B-cell pools, alteration of CD4 states, expansion of activated Tregs, and emergence of neuroimmune stress linked transcriptional modules that parallel physiological aging. Mechanistically, mitochondrial insufficiency is associated with functional loss of FOXP3-centered chromatin coordination and enrichment of NF-{kappa}B/NFAT/AP-1 inflammatory and senescence programs while lineage identity remains detectable. Partial mitochondrial attenuation within Tregs alone is sufficient to drive chronic low-grade systemic inflammation, neuromuscular decline, gut microbial restructuring, and elevated microglial responsiveness without Treg depletion. Pharmacologic and microbiota-directed interventions partially reduce inflammatory tone and improve functional metrics. Together, our findings identify TFAM as a key regulator of immune aging and reveal that healthy mitochondrial function in Tregs is essential for protecting against inflammaging and age-associated functional decline.

immunology↗

bioRxiv2022

The chemokine receptor CXCR3 promotes CD8+ T cell-dependent lung pathology during influenza pathogenesis

While the role of CD8+ T cells in influenza clearance is established, their contribution to pathological lung injury is increasingly appreciated. To explore if protective versus pathological functions can be linked to CD8+ T cell subpopulations, we dissected their responses in influenza-infected murine lungs. Our single-cell RNASeq (scRNAseq) analysis revealed significant diversity in CD8+ T cell subpopulations during peak viral load vs. infection-resolved state. While enrichment of Cxcr3hi CD8+ T effector (Teff) subset was associated with a more robust cytotoxic response, both CD8+ Teff and CD8+ T central memory (TCM) exhibited equally potent effector potential. The scRNAseq analysis identified unique regulons regulating the cytotoxic response in CD8+ T cells. The neutralization of CXCR3 mitigated lung injury without affecting viral clearance. IFN-{gamma} was dispensable to regulate the cytotoxic response of Cxcr3hi CD8+ T cells. Collectively, our data imply that CXCR3 interception could have a therapeutic effect in preventing influenza-linked lung injury. TEASERThe CXCR3 expressing CD8+ T cell subset causes severe lung pathology and exacerbates disease severity without affecting viral clearance during influenza infection

immunology↗