Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology

Singh, Amit Kumar; Kasarpalkar, Nandini; Bhowmick, Shilpa; G, Paradkar; M, Talreja; Shah, Karan; Tiwari, Abhishek; Palav, Harsha; Kaginkar, Snehal; Kulkarni, Rajiv; Patil, Ashwini; Kalsurkar, Varsha; Agrawal, Sachee; Shastri, Jayanthi; R, Dere; Bharmal, Ramesh; Mahale, Smita D.; Bhor, Vikrant M.; Patel, Vainav

doi:10.1002/jlb.3covbcr0621-300r

Cited by 7 publications

(7 citation statements)

References 48 publications

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“…In addition, we found significantly elevated IL-15 in plasma from hospitalized COVID-19 patients at equivalent levels to those previously reported [ 28 ]. IL-15 is a pro-inflammatory cytokine that induces the proliferation, survival, and function of lymphoid cell populations, particularly NK cells, and CD8 + cytotoxic T cells, as well as epithelial cells [ 29 ].…”

Section: Discussionsupporting

confidence: 89%

“…IL-15 is a pro-inflammatory cytokine that induces the proliferation, survival, and function of lymphoid cell populations, particularly NK cells, and CD8 + cytotoxic T cells, as well as epithelial cells [ 29 ]. Numerous reports have shown that IL-15 is increased in the plasma of COVID-19 patients, suggesting that IL-15 may be a marker of symptomatic progression or mortality [ 28 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

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SARS-CoV-2-Induced TSLP Is Associated with Duration of Hospital Stay in COVID-19 Patients

Gerla

Moitra

Pink

et al. 2023

Viruses

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Thymic stromal lymphopoietin (TSLP) is an epithelium-derived pro-inflammatory cytokine involved in lung inflammatory responses. Previous studies show conflicting observations in blood TSLP in COVID-19, while none report SARS-CoV-2 inducing TSLP expression in bronchial epithelial cells. Our objective in this study was to determine whether TSLP levels increase in COVID-19 patients and if SARS-CoV-2 induces TSLP expression in bronchial epithelial cells. Plasma cytokine levels were measured in patients hospitalized with confirmed COVID-19 and age- and sex-matched healthy controls. Demographic and clinical information from COVID-19 patients was collected. We determined associations between plasma TSLP and clinical parameters using Poisson regression. Cultured human nasal (HNEpC) and bronchial epithelial cells (NHBEs), Caco-2 cells, and patient-derived bronchial epithelial cells (HBECs) obtained from elective bronchoscopy were infected in vitro with SARS-CoV-2, and secretion as well as intracellular expression of TSLP was detected by immunofluorescence. Increased TSLP levels were detected in the plasma of hospitalized COVID-19 patients (603.4 ± 75.4 vs 997.6 ± 241.4 fg/mL, mean ± SEM), the levels of which correlated with duration of stay in hospital (β: 0.11; 95% confidence interval (CI): 0.01–0.21). In cultured NHBE and HBECs but not HNEpCs or Caco-2 cells, TSLP levels were significantly elevated after 24 h post-infection with SARS-CoV-2 (p < 0.001) in a dose-dependent manner. Plasma TSLP in COVID-19 patients significantly correlated with duration of hospitalization, while SARS-CoV-2 induced TSLP secretion from bronchial epithelial cells in vitro. Based on our findings, TSLP may be considered an important therapeutic target for COVID-19 treatment.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2-Induced TSLP Is Associated with Duration of Hospital Stay in COVID-19 Patients

Gerla

Moitra

Pink

et al. 2023

Viruses

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“…This prompted us to consider whether these GPR56+ cells are similar to bystander-activated virtual memory (VM) CD8+ T-cells 40 , a feature of which is their ability to be activated rapidly by inflammatory cytokines alone (e.g., IL-12 and IL-18) to produce IFNγ without T-cell receptor (TCR) stimulation 40 . VM CD8+ T-cells develop and expand in the periphery via cytokine stimulation, including IL-15 induced by viral infection (IL-15 concentrations are known to be elevated in acute COVID-19 patients and correlate with disease severity 41, 42 ), and subsequently develop a differentiated EM phenotype expressing CD45RA 40 . We assessed several reported surface markers of these cells 40 in GPR56+ vs. GPR56-cells and found that the GPR56+ cells were indeed phenotypically similar to VM cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Influenza vaccination and single cell multiomics reveal sex dimorphic immune imprints of prior mild COVID-19

Sparks¹,

Lau²,

Liu

et al. 2022

Preprint

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Viral infections can have profound and durable functional impacts on the immune system. There is an urgent need to characterize the long-term immune effects of SARS-CoV-2 infection given the persistence of symptoms in some individuals and the continued threat of novel variants including the recent rapid acceleration in infections. As the majority of COVID-19 patients experienced mild disease, here we use systems immunology approaches to comparatively assess the post-infection immune status (mean: 151 [5th - 95th percentile: 58 - 235] days after diagnosis) and subsequent innate and adaptive responses to seasonal influenza vaccination (as an "immune challenge") in 33 previously healthy individuals after recovery from mild, non-hospitalized COVID-19, as compared to 40 age- and sex-matched healthy controls with no history of COVID-19. Sex-specific, temporally stable shifts in signatures of metabolism, T-cell activation, and innate immune/inflammatory processes suggest that mild COVID-19 can establish new post-infection immunological set-points. COVID-19-recovered males had an increase in CD71hi B-cells (including influenza-specific subsets) before vaccination and more robust innate, influenza-specific plasmablast, and antibody responses after vaccination compared to healthy males. Intriguingly, by day 1 post-vaccination in COVID-19-recovered subjects, the expression of numerous innate defense/immune receptor genes (e.g., Toll-like receptors) in monocytes increased and moved away from their post-COVID-19 repressed state toward the pre-vaccination baseline of healthy controls, and these changes tended to persist to day 28 in females, hinting that the acute inflammatory responses induced by vaccination could partly reset the immune states established by prior mild COVID-19. Our study reveals sex-dimorphic immune imprints and in vivo functional impacts of mild COVID-19 in humans, suggesting that prior COVID-19 could change future responses to vaccination and in turn, vaccines could help reset the immune system after COVID-19, both in an antigen-agnostic manner.

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“…Another protein inversely correlated with serum IL-6 levels during SARS-CoV-2 infection is soluble mucosal addressin cell adhesion molecule (sMAdCAM), which is expressed by gut endothelial venules to induce migration of immune cells into the intestine ( 68 , 69 ). At the same time, sMAdCAM levels were lower in COVID-19 patients compared to healthy controls or convalescent subjects, suggesting that normalization of sMAdCAM levels may signify the restoration of mucosal homeostasis and highlighting its role as an important systemic and gut homing parameter that needs to be monitored for better therapeutic guidance and prophylactic intervention in COVID-19 ( 68 , 69 ).…”

Section: Sars-cov-2-mediated Changes In the Intestinal Immunological ...mentioning

confidence: 99%

Alterations in gut immunological barrier in SARS-CoV-2 infection and their prognostic potential

et al. 2023

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Although coronavirus disease 2019 (COVID-19) is primarily associated with mild respiratory symptoms, a subset of patients may develop more complicated disease with systemic complications and multiple organ injury. The gastrointestinal tract may be directly infected by SARS-CoV-2 or secondarily affected by viremia and the release of inflammatory mediators that cause viral entry from the respiratory epithelium. Impaired intestinal barrier function in SARS-CoV-2 infection is a key factor leading to excessive microbial and endotoxin translocation, which triggers a strong systemic immune response and leads to the development of viral sepsis syndrome with severe sequelae. Multiple components of the gut immune system are affected, resulting in a diminished or dysfunctional gut immunological barrier. Antiviral peptides, inflammatory mediators, immune cell chemotaxis, and secretory immunoglobulins are important parameters that are negatively affected in SARS-CoV-2 infection. Mucosal CD4+ and CD8+ T cells, Th17 cells, neutrophils, dendritic cells, and macrophages are activated, and the number of regulatory T cells decreases, promoting an overactivated immune response with increased expression of type I and III interferons and other proinflammatory cytokines. The changes in the immunologic barrier could be promoted in part by a dysbiotic gut microbiota, through commensal-derived signals and metabolites. On the other hand, the proinflammatory intestinal environment could further compromise the integrity of the intestinal epithelium by promoting enterocyte apoptosis and disruption of tight junctions. This review summarizes the changes in the gut immunological barrier during SARS-CoV-2 infection and their prognostic potential.

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Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology

Cited by 7 publications

References 48 publications

SARS-CoV-2-Induced TSLP Is Associated with Duration of Hospital Stay in COVID-19 Patients

SARS-CoV-2-Induced TSLP Is Associated with Duration of Hospital Stay in COVID-19 Patients

Influenza vaccination and single cell multiomics reveal sex dimorphic immune imprints of prior mild COVID-19

Alterations in gut immunological barrier in SARS-CoV-2 infection and their prognostic potential

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