Interleukin 16 Enhances the Host Susceptibility to Influenza A Virus Infection

Jia, Rong; Jiang, Congwei; Li, Long; Huang, Chenxu; Lu, Lijuan; Xu, Menghua; Xu, Jin; Liang, Xiaozhen

doi:10.3389/fmicb.2021.736449

Cited by 9 publications

(6 citation statements)

References 53 publications

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“…To do this we injected the hens with LPS, a well-known stimulator of the immune system ( Simpson and Trent, 2019 ), and compared the response to five established LPS-induced cytokines. In agreement with previous reports ( Erickson and Banks, 2011 ; Magrini et al, 2016 ; Jia et al, 2021 ), stimulation by LPS increased the expression significantly in the already established LPS-related cytokines and Pentraxin 3 ( Figure 1D ). Taken together, the significant correlation between duplicates within an array and the expected response to LPS indicate a specific recognition of the antibodies against their corresponding targets.…”

Section: Resultssupporting

confidence: 93%

A decline in avian cytokine expression with age revealed by commercially available cytokine array

et al. 2023

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Cytokines are secreted immunomodulators that are key regulators of the avian immune response. Currently, the most commonly used method to follow cytokine expression is qPCR, which measures cellular levels of mRNA, rather their extracellular circulating levels. Here we present a commercially available cytokine array designed to assay circulating expression levels of multiple cytokines and immunomodulators simultaneously. Upon minor modifications to the manufacturer protocol, background noise was reduced, leading to a significant increase in the sensitivity of the device. Our data indicate that the array is reliable and produce consistent data between biological repeats. We tested the reproducibility of the array in a biologically relevant context by assessing age-related changes in circulating cytokines. While individual features did not show a consistent pattern, our data revealed a consistent decline in the median of all cytokine values, supporting the validity of the array in studying biological processes.

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Section: Resultssupporting

confidence: 93%

A decline in avian cytokine expression with age revealed by commercially available cytokine array

et al. 2023

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“…IL-16 significantly contributes to pathologies associated with inflammation, like inflammatory bowel disease [ 43 ]. Early studies demonstrate IL-16 functions in inhibition of the replication of the human immunodeficiency virus, and in enhancing the host susceptibility to influenza A virus infection [ 44 , 45 , 46 ].…”

Section: Resultsmentioning

confidence: 99%

“…Regarding IL-16, this is the first report of a recognition of the viral E protein by this cytokine, which has known functions as a chemoattractant and activator of CD4 + T-cells. IL-16 is included in a four-biomarker blood signature that discriminates host systemic inflammation caused by a viral infection from other etiologies [ 46 ]. It is noteworthy that a significant increase in the levels of IL-16 is observed in the serum and cerebrospinal fluid of patients with COVID-19 [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Host PDZ-Based Interactions with the SARS-CoV-2 E Protein in Human Monocytes

Ávila-Flores,

Sánchez-Cabezón,

Ochoa-Echeverría

et al. 2023

IJMS

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Proteins containing PDZ (post-synaptic density, PSD-95/disc large, Dlg/zonula occludens, ZO-1) domains assemble signaling complexes that orchestrate cell responses. Viral pathogens target host PDZ proteins by coding proteins containing a PDZ-binding motif (PBM). The presence of a PBM in the SARS-CoV-2 E protein contributes to the virus’s pathogenicity. SARS-CoV-2 infects epithelia, but also cells from the innate immune response, including monocytes and alveolar macrophages. This process is critical for alterations of the immune response that are related to the deaths caused by SARS-CoV-2. Identification of E-protein targets in immune cells might offer clues to understanding how SARS-CoV-2 alters the immune response. We analyzed the interactome of the SARS-CoV-2 E protein in human monocytes. The E protein was expressed fused to a GFP tag at the amino terminal in THP-1 monocytes, and associated proteins were identified using a proteomic approach. The E-protein interactome provided 372 partners; only 8 of these harbored PDZ domains, including the cell polarity protein ZO-2, the chemoattractant IL-16, and syntenin. We addressed the expression and localization of the identified PDZ proteins along the differentiation of primary and THP-1 monocytes towards macrophages and dendritic cells. Our data highlight the importance of identifying the functions of PDZ proteins in the maintenance of immune fitness and the viral alteration of inflammatory response.

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“…Indeed, IL16 has been extensively studied for its ability to inhibit human immunodeficiency virus (HIV) replication, partly by suppressing mRNA expression (Baier et al 1995; Zhou et al 1997; Idziorek et al 1998). Additionally, but in contrast to its HIV-suppressive properties, IL16 can enhance the replication of influenza A virus (IAV) and facilitate its infection of hosts, potentially through its repression of type I interferon beta and interferon-stimulated genes (Jia et al 2021). IL16 can also contribute to the establishment of lifelong gamma herpesvirus infection (Liu et al 2020).…”

Section: Discussionmentioning

confidence: 99%

An eQTL-based Approach Reveals Candidate Regulators of LINE-1 RNA Levels in Lymphoblastoid Cells

Bravo,

Mizrahi,

Kim

et al. 2023

Preprint

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Long interspersed element 1 (L1) are a family of autonomous, actively mobile transposons that occupy ~17% of the human genome. The pleiotropic effects L1 induces in host cells - promoting genome instability, inflammation, or cellular senescence - are established, and L1's associations with aging and aging diseases are widely recognized. However, because of the cell type-specific nature of transposon control, the catalogue of L1 regulators remains incomplete. Here, we employ an eQTL approach leveraging transcriptomic and genomic data from the GEUVADIS and 1000Genomes projects to computationally identify new candidate regulators of L1 expression in lymphoblastoid cell lines. To cement the role of candidate genes in L1 regulation, we experimentally modulate the levels of top candidates in vitro, including IL16, STARD5, HSDB17B12, and RNF5, and assess changes in TE family expression by Gene Set Enrichment Analysis (GSEA). Remarkably, we observe subtle but widespread upregulation of TE family expression following IL16 and STARD5 overexpression. Moreover, a short-term 24 hour exposure to recombinant human IL16 was sufficient to transiently induce subtle but widespread upregulation of L1 subfamilies. Finally, we find that many L1 expression-associated genetic variants are co-associated with aging traits across genome-wide association study databases. Our results expand the catalogue of genes implicated in L1 transcriptional control and further suggest that L1 contributes to aging processes. Given the ever-increasing availability of paired genomic and transcriptomic data, we anticipate this new approach to be a starting point for more comprehensive computational scans for transposon transcriptional regulators.

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Interleukin 16 Enhances the Host Susceptibility to Influenza A Virus Infection

Cited by 9 publications

References 53 publications

A decline in avian cytokine expression with age revealed by commercially available cytokine array

A decline in avian cytokine expression with age revealed by commercially available cytokine array

Identification of Host PDZ-Based Interactions with the SARS-CoV-2 E Protein in Human Monocytes

An eQTL-based Approach Reveals Candidate Regulators of LINE-1 RNA Levels in Lymphoblastoid Cells

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