Wnt-β-Catenin Signaling in Human Dendritic Cells Mediates Regulatory T-Cell Responses to Fungi via the PD-L1 Pathway

Karnam, Anupama; Bonam, Srinivasa Reddy; Rambabu, Naresh; Wong, Sarah Sze Wah; Aimanianda, Vishukumar; Bayry, Jagadeesh

doi:10.1128/mbio.02824-21

Cited by 22 publications

(16 citation statements)

References 82 publications

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“…It has also emerged as an integral component of host responses to infection but its function in the context of immune responses is not fully understood (68–70). Recent studies have shown that this pathway can control host processes related to bacterial infection; however, pathogens have evolved strategies to manipulate Wnt-associated processes in order to enhance infection and survival within the human host (68–70). The mitogen-activated protein kinase (MAPK) signalling pathway was the second most enriched pathway by this set of genes.…”

Section: Resultsmentioning

confidence: 99%

“…This pathway contributes to the cell cycle control, cytoskeleton reorganization during phagocytosis and cell migration, autophagy, apoptosis, and a number of other inflammation-related events (68). It has also emerged as an integral component of host responses to infection but its function in the context of immune responses is not fully understood (68)(69)(70). Recent studies have shown that this pathway can control host processes related to bacterial infection; however, pathogens have evolved strategies to manipulate Wntassociated processes in order to enhance infection and survival within the human host (68)(69)(70).…”

Section: Resultsmentioning

confidence: 99%

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dSeqSb: A systems biology approach to decipher dynamics of host-pathogen interactions using temporal dual RNA-seq data

Dinarvand

Koch

Mouiee

et al. 2022

Preprint

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Infection triggers a dynamic cascade of reciprocal events between host and pathogen wherein the host activates complex mechanisms to recognise and kill pathogens while the pathogen adjusts its virulence and fitness to avoid eradication by the host. The interaction between the pathogen and the host results in large-scale changes in gene expression in both organisms. Dual RNA-seq, the simultaneous detection of host and pathogen transcripts, has become a leading approach to unravel complex molecular interactions between the host and the pathogen and is particularly informative for intracellular organisms. The amount of in vitro and in vivo dual RNA-seq data is rapidly growing which demands computational pipelines to effectively analyse such data. In particular, holistic, systems-level, and temporal analyses of dual RNA-seq data are essential to enable further insights into the host-pathogen transcriptional dynamics and potential interactions. Here, we developed an integrative network-driven bioinformatics pipeline, dRNASb, a systems biology-based computational pipeline to analyse temporal transcriptional clusters, incorporate molecular interaction networks (e.g., protein-protein interactions), identify topologically and functionally key transcripts in host and pathogen, and associate host and pathogen temporal transcriptome to decipher potential between-species interactions. The pipeline is applicable to various dual RNA-seq data from different species and experimental conditions. As a case study, we applied dRNASb to analyse temporal dual RNA-seq data of Salmonella-infected human cells, which enabled us to uncover genes contributing to the infection process and their potential functions and to identify potential host-pathogen interactions between host and pathogen genes. Overall, dRNASb has the potential to identify key genes involved in bacterial growth or host defence mechanisms for future uses as therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

dSeqSb: A systems biology approach to decipher dynamics of host-pathogen interactions using temporal dual RNA-seq data

Dinarvand

Koch

Mouiee

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…This pathway contributes to the cell cycle control, cytoskeleton reorganisation during phagocytosis and cell migration, autophagy, apoptosis, and a number of other inflammation-related events [66]. It has also emerged as an integral component of host responses to infection, but its function in the context of immune responses is not fully understood [66][67][68]. Recent studies have shown that this pathway can control host processes related to bacterial infection; however, pathogens have evolved strategies to manipulate Wnt-associated processes in order to enhance infection and survival within the human host [66][67][68].…”

Section: Resultsmentioning

confidence: 99%

dRNASb: a systems biology approach to decipher dynamics of host-pathogen interactions using temporal dual RNA-seq data

et al. 2022

View full text Add to dashboard Cite

Infection triggers a dynamic cascade of reciprocal events between host and pathogen wherein the host activates complex mechanisms to recognise and kill pathogens while the pathogen often adjusts its virulence and fitness to avoid eradication by the host. The interaction between the pathogen and the host results in large-scale changes in gene expression in both organisms. Dual RNA-seq, the simultaneous detection of host and pathogen transcripts, has become a leading approach to unravelling complex molecular interactions between the host and the pathogen and is particularly informative for intracellular organisms. The amount of in vitro and in vivo dual RNA-seq data is rapidly growing, which demands computational pipelines to effectively analyse such data. In particular, holistic, systems-level, and temporal analyses of dual RNA-seq data are essential to enable further insights into the host-pathogen transcriptional dynamics and potential interactions. Here, we developed an integrative network-driven bioinformatics pipeline, dRNASb, a systems biology-based computational pipeline to analyse temporal transcriptional clusters, incorporate molecular interaction networks (e.g. protein-protein interactions), identify topologically and functionally key transcripts in host and pathogen, and associate host and pathogen temporal transcriptome to decipher potential between-species interactions. The pipeline is applicable to various dual RNA-seq data from different species and experimental conditions. As a case study, we applied dRNASb to analyse temporal dual RNA-seq data of Salmonella -infected human cells, which enabled us to uncover genes contributing to the infection process and their potential functions and to identify putative associations between host and pathogen genes during infection. Overall, dRNASb has the potential to identify key genes involved in bacterial growth or host defence mechanisms for future uses as therapeutic targets.

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“…However, immune exhaustion by signaling through checkpoint molecules could prevent effective clearance of the pathogens leading to exacerbated immune responses (44,45). PD-L1 and PD-1 interaction also supports regulatory T cell responses (46)(47)(48)(49)(50). Of note, PD-L1 expression was significantly higher in a group of severe COVID-19 patients as compared to milder patients and was positively correlated with the WHO and Sequential Organ Failure Assessment (SOFA) clinical scores (22).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Induces Cytokine Responses in Human Basophils

et al. 2022

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Basophils play a key role in the orientation of immune responses. Though the interaction of SARS-CoV-2 with various immune cells has been relatively well studied, the response of basophils to this pandemic virus is not characterized yet. In this study, we report that SARS-CoV-2 induces cytokine responses and in particular IL-13, in both resting and IL-3 primed basophils. The response was prominent under IL-3 primed condition. However, either SARS-CoV-2 or SARS-CoV-2-infected epithelial cells did not alter the expression of surface markers associated with the activation of basophils, such as CD69, CD13 and/or degranulation marker CD107a. We also validate that human basophils are not permissive to SARS-CoV-2 replication. Though increased expression of immune checkpoint molecule PD-L1 has been reported on the basophils from COVID-19 patients, we observed that SARS-CoV-2 does not induce PD-L1 on the basophils. Our data suggest that basophil cytokine responses to SARS-CoV-2 might help in reducing the inflammation and also to promote antibody responses to the virus.

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Wnt-β-Catenin Signaling in Human Dendritic Cells Mediates Regulatory T-Cell Responses to Fungi via the PD-L1 Pathway

Abstract: The balance between effector CD4 + T-cell and immunosuppressive regulatory T-cell (Treg) responses determines the outcome of an infectious disease. The signaling pathways that regulate human CD4 + T-effector versus Treg responses to the fungi are not completely understood.

Cited by 22 publications

References 82 publications

dSeqSb: A systems biology approach to decipher dynamics of host-pathogen interactions using temporal dual RNA-seq data

dSeqSb: A systems biology approach to decipher dynamics of host-pathogen interactions using temporal dual RNA-seq data

dRNASb: a systems biology approach to decipher dynamics of host-pathogen interactions using temporal dual RNA-seq data

SARS-CoV-2 Induces Cytokine Responses in Human Basophils

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