Dataset Information

Proteomic investigation reveals dominant alterations of neutrophil degranulation and mRNA translation pathways in patients with COVID-19.

ABSTRACT: The altered molecular proteins and pathways in response to COVID-19 infection are still unclear. Here, we performed a comprehensive proteomics-based investigation of nasopharyngeal swab samples from patients with COVID-19 to study the host response by employing simple extraction strategies. Few of the host proteins such as interleukin-6, L-lactate dehydrogenase, C-reactive protein, Ferritin, and aspartate aminotransferase were found to be upregulated only in COVID-19-positive patients using targeted multiple reaction monitoring studies. The most important pathways identified by enrichment analysis were neutrophil degranulation, interleukin-12 signaling pathways, and mRNA translation of proteins thus providing the detailed investigation of host response in COVID-19 infection. Thus, we conclude that mass spectrometry-detected host proteins have a potential for disease severity progression; however, suitable validation strategies should be deployed for the clinical translation. Furthermore, the in silico docking of potential drugs with host proteins involved in the interleukin-12 signaling pathway might aid in COVID-19 therapeutic interventions.

SUBMITTER: Bankar R

PROVIDER: S-EPMC7857979 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proteomic investigation reveals dominant alterations of neutrophil degranulation and mRNA translation pathways in patients with COVID-19.

Bankar Renuka R Suvarna Kruthi K Ghantasala Saicharan S Banerjee Arghya A Biswas Deeptarup D Choudhury Manisha M Palanivel Viswanthram V Salkar Akanksha A Verma Ayushi A Singh Avinash A Mukherjee Amrita A Pai Medha Gayathri J MGJ Roy Jyotirmoy J Srivastava Alisha A Badaya Apoorva A Agrawal Sachee S Shrivastav Om O Shastri Jayanthi J Srivastava Sanjeeva S

iScience 20210204 3

The altered molecular proteins and pathways in response to COVID-19 infection are still unclear. Here, we performed a comprehensive proteomics-based investigation of nasopharyngeal swab samples from patients with COVID-19 to study the host response by employing simple extraction strategies. Few of the host proteins such as interleukin-6, L-lactate dehydrogenase, C-reactive protein, Ferritin, and aspartate aminotransferase were found to be upregulated only in COVID-19-positive patients using targ ...[more]

PMID: 33558857

Similar Datasets

Project description:IntroductionMultiple sclerosis (MS) is a chronic and debilitating inflammatory disease of the central nervous system (CNS), characterized by demyelination and neurodegeneration. Emerging evidence implicates neutrophils in MS pathogenesis, particularly through processes like neutrophil extracellular traps (NETs) formation and degranulation, which may exacerbate inflammation and autoimmunity.MethodsRNA sequencing of peripheral blood neutrophils from MS patients and healthy controls identified differentially expressed genes (DEGs). Pathway enrichment and protein-protein interaction (PPI) analyses highlighted potential biomarkers, validated using reverse transcription quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA).ResultsOur analysis identified 1,968 DEGs in neutrophils from MS patients, comprising 1,068 upregulated and 900 downregulated genes. Pathway enrichment analysis revealed significant involvement of immune processes, including antigen presentation, B and T cell receptor signaling, intracellular signaling cascades, and neutrophil degranulation. Notably, KEGG analysis highlighted a pivotal role for upregulated genes in neutrophil extracellular traps (NETs) formation, a process increasingly associated with autoimmunity. PPI network analysis pinpointed five key hub genes-LCN2, LTF, ELANE, CAMP, and CTSG-as central players in neutrophil-mediated immune modulation. Protein-level validation using ELISA confirmed elevated levels of LCN2, ELANE, CAMP, and CTSG, consistent with transcriptomic findings, further supporting their role as biomarkers. Subsequent RT-qPCR validation demonstrated robust diagnostic potential for these genes, with area under the curve (AUC) values of 0.952 (LCN2), 0.827 (LTF), 0.968 (ELANE), 0.950 (CAMP), and 0.862 (CTSG).DiscussionThese findings uncover a previously underappreciated role for neutrophils in MS pathogenesis, driven by alterations in gene expression linked to immune modulation and NET formation. The identified biomarkers, particularly ELANE and LCN2, demonstrate strong diagnostic potential, offering a new avenue for non-invasive MS diagnostics. Beyond clinical utility, this study highlights the importance of neutrophil-driven immune responses in MS, providing mechanistic insights into the complex interplay between innate and adaptive immunity in demyelinating diseases. Furthermore, these findings suggest that targeting neutrophil-specific processes, such as NETs formation and degranulation, could mitigate inflammatory damage and provide novel therapeutic approaches for MS treatment. These results lay the groundwork for future studies exploring therapeutic strategies targeting neutrophil functions in MS.

Project description:Myocardial infarction (MI) is one of the most common cardiac emergencies with high morbidity and is a leading cause of death worldwide. Since MI could develop into a life-threatening emergency and could also seriously affect the life quality of patients, continuous efforts have been made to create an effective strategy to prevent the occurrence of MI and reduce MI-related mortality. Numerous studies have confirmed that neutrophils play important roles in inflammation and innate immunity, which provide the first line of defense against microorganisms by producing inflammatory cytokines and chemokines, releasing reactive oxygen species, and degranulating components of neutrophil cytoplasmic granules to kill pathogens. Recently, researchers reported that neutrophils are closely related to the severity and prognosis of patients with MI, and neutrophil to lymphocyte ratio in post-MI patients had predictive value for major adverse cardiac events. Neutrophils have been increasingly recognized to exert important functions in MI. Especially, granule proteins released by neutrophil degranulation after neutrophil activation have been suggested to involve in the process of MI. This article reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Video abstract Neutrophils played a crucial role throughout the process of MI, and neutrophil degranulation was the crucial step for the regulative function of neutrophils. Both neutrophils infiltrating and neutrophil degranulation take part in the injury and repair process immediately after the onset of MI. Since different granule subsets (e g. MPO, NE, NGAL, MMP-8, MMP-9, cathelicidin, arginase and azurocidin) released from neutrophil degranulation show different effects through diverse mechanisms in MI. In this review, we reviewed the current research progress of neutrophil granules in MI and discusses neutrophil degranulation associated diagnosis and treatment strategies. Myeloperoxidase (MPO); Neutrophil elastase (NE); Neutrophil gelatinase-associated lipocalin (NGAL); Matrix metalloproteinase 8 (MMP-8); Matrix metalloproteinase 9 (MMP-9).

Project description:BackgroundMalaria caused by Plasmodium falciparum results in severe complications including cerebral malaria (CM) especially in children. While the majority of falciparum malaria survivors make a full recovery, there are reports of some patients ending up with neurological sequelae or cognitive deficit.MethodsAn analysis of pooled transcriptome data of whole blood samples derived from two studies involving various P. falciparum infections, comprising mild malaria (MM), non-cerebral severe malaria (NCM) and CM was performed. Pathways and gene ontologies (GOs) elevated in the distinct P. falciparum infections were determined.ResultsIn all, 2876 genes were expressed in common between the 3 forms of falciparum malaria, with CM having the least number of expressed genes. In contrast to other research findings, the analysis from this study showed MM share similar biological processes with cancer and neurodegenerative diseases, NCM is associated with drug resistance and glutathione metabolism and CM is correlated with endocannabinoid signalling and non-alcoholic fatty liver disease (NAFLD). GO revealed the terms biogenesis, DNA damage response and IL-10 production in MM, down-regulation of cytoskeletal organization and amyloid-beta clearance in NCM and aberrant signalling, neutrophil degranulation and gene repression in CM. Differential gene expression analysis between CM and NCM showed the up-regulation of neutrophil activation and response to herbicides, while regulation of axon diameter was down-regulated in CM.ConclusionsResults from this study reveal that P. falciparum-mediated inflammatory and cellular stress mechanisms may impair brain function in MM, NCM and CM. However, the neurological deficits predominantly reported in CM cases could be attributed to the down-regulation of various genes involved in cellular function through transcriptional repression, axonal dysfunction, dysregulation of signalling pathways and neurodegeneration. It is anticipated that the data from this study, might form the basis for future hypothesis-driven malaria research.

Dataset Information

Proteomic investigation reveals dominant alterations of neutrophil degranulation and mRNA translation pathways in patients with COVID-19.

Publications

Proteomic investigation reveals dominant alterations of neutrophil degranulation and mRNA translation pathways in patients with COVID-19.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets