Biology subjects

Smita, S.

Publications and source records attributed to Smita, S..

5 recordsLinked to original sources

bioRxiv2023

NAIP-NLRC4 Inflammasome Activation in Tuft Cells Activates a PGD2-ILC3 Signaling Circuit that Protects Against Enteric Infection.

Intestinal epithelial cells (IEC) use innate sensing pathways to distinguish pathogens from commensals. One such pathway, the NAIP--NLRC4 inflammasome, initiates extrusion of infected IEC and mediator release upon cytosolic bacterial sensing. Tuft cells are primarily known for their function in anti-parasite immunity. We previously reported that activation of the inflammasome in tuft cells leads to release of prostaglandin D2 (PGD2). We test the hypothesis that tuft cell specific release of PGD2 after inflammasome activation initiates antibacterial responses. NAIP--NLRC4 inflammasome activation in tuft cells leads to a type 3 antimicrobial response with increased IL-22 and antimicrobial protein levels within the small intestine, which is dependent on PGD2 signaling. A subset of ILC3 express the PGD2 receptor CRTH2 and we show them as the source of the increased IL-22. Inflammasome activation in tuft cells also leads to better control of Salmonella Typhimurium. These data support that intestinal tuft cells can also induce antibacterial responses. SummaryPGD2 release after NAIP--NLRC4 inflammasome activation in tuft cells signals onto ILC3s and mediates host defense mechanisms against Salmonella Typhimurium within the small intestine. Tuft cells therefore not only promote immune reactions against parasites, but also bacteria.

immunology↗

bioRxiv2021

NCoR1 and SMRT fine-tune inflammatory versus tolerogenic balance in dendritic cells by differentially regulating STAT3 signaling

Dendritic cell (DC) fine-tunes inflammatory versus tolerogenic responses to protect from immune-pathology. However, the role of co-regulators in maintaining this balance is unexplored. NCoR1-mediated repression of DC immune-tolerance has been recently reported. Here we found that depletion of NCoR1 paralog SMRT (NCoR2) enhanced cDC1 activation and expression of IL-6, IL-12 and IL-23 while concomitantly decreasing IL-10 expression/secretion. Consequently, co-cultured CD4+ and CD8+ T-cells depicted enhanced Th1/Th17 frequency and cytotoxicity, respectively. Comparative genomic and transcriptomic analysis demonstrated differential regulation of IL-10 by SMRT and NCoR1. SMRT depletion represses mTOR-STAT3-IL10 signaling in cDC1 by downregulating NR4A1. Besides, Nfkbia and Socs3 were down-regulated in Ncor2 (Smrt) knockdown cDC1, supporting increased production of inflammatory cytokines. Moreover, studies in mice showed, adoptive transfer of SMRT knockdown cDC1 in OVA-DTH induced footpad inflammation led to increased Th1/Th17 and reduced tumor burden after B16 melanoma injection by enhancing oncolytic CD8+ T-cell frequency, respectively. We also depicted decreased Ncor2 expression in Rheumatoid Arthritis, a Th1/Th17 disease.

immunology↗

bioRxiv2020

SARS-CoV2 genome analysis of Indian isolates and molecular modelling of D614G mutated spike protein with TMPRSS2 depicted its enhanced interaction and virus infectivity

COVID-19 that emerged as a global pandemic is caused by SARS-CoV-2 virus. The virus genome analysis during disease spread reveals about its evolution and transmission. We did whole genome sequencing of 225 clinical strains from the state of Odisha in eastern India using ARTIC protocol-based amplicon sequencing. Phylogenetic analysis identified the presence of all five reported clades 19A, 19B, 20A, 20B and 20C in the population. The analyses revealed two major routes for the introduction of the disease in India i.e. Europe and South-east Asia followed by local transmission. Interestingly, 19B clade was found to be much more prevalent in our sequenced genomes (17%) as compared to other genomes reported so far from India. The haplogroup analysis for clades showed evolution of 19A and 19B in parallel whereas the 20B and 20C appeared to evolve from 20A. Majority of the 19A and 19B clades were present in cases that migrated from Gujarat state in India suggesting it to be one of the major initial points of disease transmission in India during month of March and April. We found that with the time 20A and 20B clades evolved drastically that originated from central Europe. At the same time, it has been observed that 20A and 20B clades depicted selection of four common mutations i.e. 241 C>T (5UTR), P323L in RdRP, F942F in NSP3 and D614G in the spike protein. We found an increase in the concordance of G614 mutation evolution with the viral load in clinical samples as evident from decreased Ct value of spike and Orf1ab gene in qPCR. Molecular modelling and docking analysis identified that D614G mutation enhanced interaction of spike with TMPRSS2 protease, which could impact the shedding of S1 domain and infectivity of the virus in host cells.

genomics↗

bioRxiv2020

The Atlas of Inflammation-Resolution (AIR)

Acute inflammation is a protective reaction by the immune system in response to invading pathogens or tissue damage. Ideally, the response should be localized, self-limited, and returning to homeostasis. If not resolved, acute inflammation can result in organ pathologies leading to chronic inflammatory phenotypes. Acute inflammation and inflammation resolution are complex coordinated processes, involving a number of cell types, interacting in space and time. The biomolecular complexity and the fact that several biomedical fields are involved, make a multi and interdisciplinary approach necessary. This Atlas of Inflammation Resolution (AIR) is a web-based resource capturing the state-of-the-art in acute inflammation and inflammation resolution research. The AIR provides an interface for users to search thousands of interactions, arranged in inter-connected multi-layers of process diagrams, covering a wide range of clinically relevant phenotypes. The AIR serves as an open access knowledgebase, including a gateway to numerous public databases. It is furthermore possible for the user to map experimental data onto the molecular interaction maps of the AIR, providing the basis for bioinformatics analyses and systems biology approaches. By mapping experimental data onto the Atlas, it can be used to elucidate drug action as well as molecular mechanisms underlying different disease phenotypes. For the visualization and exploration of information, the AIR uses the Minerva platform, which is a well-established tool for the presentation of disease maps. The molecular details of the AIR are encoded using international standards. The Atlas of Inflammation Resolution was created as a freely accessible resource, supporting research and education in the fields of acute inflammation and inflammation resolution. The AIR connects research communities, facilitates clinical decision making, and supports research scientists in the formulation and validation of hypotheses.

immunology↗

bioRxiv2019

Gene regulatory networks associated with lateral root and nodule development in soybean

Legume plants such as soybean produce two major types of root lateral organs, lateral roots and root nodules. A robust computational framework was developed to predict potential gene regulatory networks (GRNs) associated with root lateral organ development in soybean. A genome-scale expression dataset was obtained from soybean root nodules and lateral roots and subjected to biclustering using QUBIC. Biclusters (BCs) and transcription factor (TF) genes with enriched expression in lateral root tissues were converged using different network inference algorithms to predict high confident regulatory modules that are repeatedly retrieved in different methods. The ranked combination of results from all different network inference algorithms into one ensemble solution identified 21 GRN modules of 182 co-regulated genes networks potentially involved in root lateral organ development stages in soybean. The pipeline correctly predicted previously known nodule- and LR-associated TFs including the expected hierarchical relationships. The results revealed high scorer AP2, GRF5, and C3H co-regulated GRN modules during early nodule development; and GRAS, LBD41, and ARR18 co-regulated GRN modules late during nodule maturation. Knowledge from this work supported by experimental validation in the future is expected to help determine key gene targets for biotechnological strategies to optimize nodule formation and enhance nitrogen fixation.

plant biology↗