Biology subjects

Dutt, R.

Publications and source records attributed to Dutt, R..

3 recordsLinked to original sources

bioRxiv2025

LFA-1 Interaction with GBP-130 on Plasmodium falciparum-infected Red Blood Cells mediates NK Cell Activation and Parasite Control

Natural Killer (NK) cells contribute to early immunity against Plasmodium falciparum by recognizing and eliminating infected red blood cells (iRBCs), a process mediated in part by the integrin LFA-1. However, the cognate parasite ligand for LFA-1 has remained unknown. Here, we identify Glycophorin Binding Protein-130 (PfGBP-130) as a surface-expressed ligand on iRBCs that binds the I-domain of LFA-1 (LFA-1 I). Using an LFA-1 I-Fc fusion protein, we demonstrate stage-specific binding to iRBCs, and LC-MS/MS analysis of immunopreciptates of I-Fc bound to iRBC revealed PfGBP-130 as a high-confidence interactor. Recombinant PfGBP-130 binds NK and THP-1 cells in an LFA-1-dependent manner. Co-culture assays show that PfGBP-130 promotes NK cell activation, degranulation, and facilitates contact-dependent killing of iRBCs. Neutralizing antibodies against PfGBP-130 significantly impair these responses. Our findings establish PfGBP-130 as the LFA-1 ligand on iRBCs, providing new insight into NK cell-mediated immunity in malaria and identifying a potential target for host-directed interventions.

immunology↗

bioRxiv2024

Higher amplitudes of visual networks are associated with trait but not state- depression.

Despite depression being a leading cause of global disability, neuroimaging studies have struggled to identify replicable neural correlates of depression or explain limited variance. This challenge may, in part, stem from the intertwined state (current symptoms; variable) and trait (general propensity; stable) experiences of depression. Here, we sought to disentangle state from trait experiences of depression by leveraging a longitudinal cohort and stratifying individuals into four groups: those in remission ( trait depression group), those with large longitudinal severity changes in depression symptomatology ( state depression group), and their respective matched control groups (total analytic n=1,030). We hypothesized that spatial network organization would be linked to trait depression due to its temporal stability, whereas functional connectivity between networks would be more sensitive to state-dependent depression symptoms due to its capacity to fluctuate. We identified 15 large-scale probabilistic functional networks from resting-state fMRI data and performed group comparisons on the amplitude, connectivity, and spatial overlap between these networks, using matched control participants as reference. Our findings revealed higher amplitude in visual networks for the trait depression group at the time of remission, in contrast to controls. This observation may suggest altered visual processing in individuals predisposed to developing depression over time. No significant group differences were observed in any other network measures for the trait-control comparison, nor in any measures for the state-control comparison. These results underscore the overlooked contribution of visual networks to the psychopathology of depression and provide evidence for distinct neural correlates between state and trait experiences of depression.

neuroscience↗

bioRxiv2024

A Mycobacterium tuberculosis secreted virulence factor disrupts host snRNP biogenesis

We earlier reported that Mycobacterium tuberculosis (Mtb) alters host RNA splicing to help its intracellular growth. Here, we report an unprecedented mechanism whereby a secreted virulence factor from Mtb interferes with the biogenesis of key spliceosomal components, causing an altered RNA splicing pattern. A high-throughput yeast-2-hybrid screen identified several Mtb-secreted proteins that can interact with the host RNA splicing factors (SFs). Through custom-designed in-cell assays, we show that one of those proteins, Rv1435c, targets specific exon-skipping events to alter RNA splicing. We show that Rv14345c or host splicing regulator 1 (hsr1) facilitates direct interaction between Mtb phagosomes and U5 snRNA and SNRPF, key components of the snRNPs. Genetic deletion of hsr1 reverses the specific exon-skipping events caused by WT Mtb infection. The{Delta} hsr1 strain shows compromised growth during ex vivo infection in the macrophages and in vivo infection in the mice. Tissue sections from the WT Mtb or{Delta} hsr1-infected mice showed significant hsr1-dependent SNRPF staining, a phenomenon also noted in the human intestinal tuberculosis (ITB) biopsies. We infer that hsr1 is a virulence factor which alters RNA splicing by interacting with U5snRNA and SNRPF. The splicing regulators from the host and pathogen are novel targets for anti-tuberculosis therapy.

molecular biology↗