Circulating Adaptive Immune Cells Expressing the Gut Homing Marker α4β7 Integrin Are Decreased in COVID-19

Müller, Tanja M.; Becker, Emily; Wiendl, Maximilian; Schulze, Lisa Lou; Voskens, Caroline J.; Völkl, Simon; Kremer, Andreas E.; Neurath, Markus F.; Zundler, Sebastian

doi:10.3389/fimmu.2021.639329

Cited by 9 publications

(6 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also noted a heretofore unreported positive correlation of sMAdCAM levels with CD8+ effector memory T cell counts (Supplementary Figure S4A). This observation concurs with recent data 36 demonstrating lower counts of CD8+ memory T cellsexpressing receptors for sMAdCAM (integrin α4β7) in COVID‐19. Taken together, these results highlight a clear role for altered mucosal homing in the pathogenesis of this disease.…”

Section: Resultssupporting

confidence: 93%

“…We also noted a heretofore unreported positive correlation of sMAd-CAM levels with CD8+ effector memory T cell counts (Supplementary Figure S4A). This observation concurs with recent data 36 reported for severe and ICU patients. 37 In our study we also observed increased plasma LPS levels in hypoxemic individuals compared to seronegative controls (Supplementary Figure S4B) as opposed to our previous work with a cohort of mild COVID-19.…”

Section: Contribution Of Smadcam and Il-6 To Covid-19 Associated Lymp...supporting

confidence: 94%

See 1 more Smart Citation

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

Singh

Kasarpalkar

Bhowmick

et al. 2022

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Immune cell dysregulation and lymphopenia characterize COVID‐19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study, we evaluated the association of circulating IL‐6, soluble mucosal addressin cell adhesion molecule (sMAdCAM), and IL‐15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID‐19. A cohort of SARS‐CoV‐2 infected individuals (n = 130) at various stages of disease progression together with healthy controls (n = 16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in‐depth immune subset characterization and to measure plasma IL‐6 levels. sMAdCAM, IL‐15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells, were observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL‐6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho‐depletion suggesting opposing roles in pathogenesis. Interestingly, IL‐15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, plasma IL‐15 levels negatively correlated with T, B, and NK count suggesting a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL‐15 and IL‐6, but not sMAdCAM, were associated with a longer duration of hospitalization.

show abstract

Section: Resultssupporting

confidence: 93%

Section: Contribution Of Smadcam and Il-6 To Covid-19 Associated Lymp...supporting

confidence: 94%

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

Singh

Kasarpalkar

Bhowmick

et al. 2022

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…First, we demonstrated that all RBD-specific mBCs, irrespective of the infection/vaccination context, express the β1 or β7 chain of integrins that are critical determinants of mucosal homing imprinting, with a clear dominance of an airway-homing signature. The latter observation is coherent with the study of Müller and colleagues ( 64 ) reporting reduction of α4β7-expressing memory T cells in COVID-19 patients, including those presenting with intestinal symptoms. Because circulating mBCs have been reported to return to the tissue where they were originally generated ( 65 ), our present finding suggested that mucosae of the upper respiratory tract would be prominent sites for induction of mBC not only in the context of infection but also in response to parenteral vaccination.…”

Section: Discussionsupporting

confidence: 91%

Prior SARS-CoV-2 infection enhances and reshapes spike protein–specific memory induced by vaccination

et al. 2023

View full text Add to dashboard Cite

The diversity of vaccination modalities and infection history are both variables that have an impact on the immune memory of individuals vaccinated against SARS-CoV-2. To gain more accurate knowledge of how these parameters imprint on immune memory, we conducted a long-term follow-up of SARS-CoV-2 spike protein–specific immune memory in unvaccinated and vaccinated COVID-19 convalescent individuals as well as in infection-naïve vaccinated individuals. Here, we report that individuals from the convalescent vaccinated (hybrid immunity) group have the highest concentrations of spike protein–specific antibodies at 6 months after vaccination. As compared with infection-naïve vaccinated individuals, they also display increased frequencies of an atypical mucosa-targeted memory B cell subset. These individuals also exhibited enhanced T H 1 polarization of their SARS-CoV-2 spike protein–specific follicular T helper cell pool. Together, our data suggest that prior SARS-CoV-2 infection increases the titers of SARS-CoV-2 spike protein–specific antibody responses elicited by subsequent vaccination and induces modifications in the composition of the spike protein–specific memory B cell pool that are compatible with enhanced functional protection at mucosal sites.

show abstract

“…Interestingly, we detected a decreased level of ITGA4 (CD49d) mRNA in the severe patients, including those with cardiovascular involvement. This finding is consistent with the reported decrease in the levels of CD49d in adults with severe COVID-19 [ 33 ], suggesting that CD49d might also be a biomarker of worse disease progression in pediatric patients.…”

Section: Discussionsupporting

confidence: 92%

The Immunological Profile of SARS-CoV-2 Infection in Children Is Linked to Clinical Severity and Age

Vanetti

Lampasona

Stracuzzi

et al. 2023

IJMS

View full text Add to dashboard Cite

Coronavirus disease 19 (COVID-19) is clinically less severe in children, even if the wide variety and degree of severity of symptoms reported in children pose a still-unresolved challenge for clinicians. We performed an in-depth analysis of the immunological profiles of 18 hospitalized SARS-CoV-2-infected children, whose results were compared to those obtained from 13 age- and sex-matched healthy controls (HC). The patients were categorized as paucisymptomatic/moderate (55.6%) or severe/critical (44.5%) according to established diagnostic criteria and further stratified into the categories of infants (1–12 months), children (1–12 years), and adolescents (>12 years). We assessed SARS-CoV-2-specific RBD antibodies (Ab), neutralizing antibodies (nAb), and circulating cytokines/chemokines in the plasma, and the SARS-CoV-2-specific immune response was measured in PBMCs by gene expression and secretome analyses. Our results showed peculiar circulating cytokine/chemokine profiles among patients sharing a similar clinical phenotype. A cluster of patients consisting of infants with severe symptoms presented hyperinflammatory profiles, together with extremely polarized antibody profiles. In a second cluster consisting of paucisymptomatic patients, a less pronounced increase in the level of inflammatory cytokines, together with an association between the selected cytokines and humoral responses, was observed. A third cluster, again consisting of paucisymptomatic patients, showed a circulating cytokine/chemokine profile which overlapped with that of the HC. The SARS-CoV-2-stimulated production of pro-inflammatory proteins, T lymphocyte activation, and migration-specific proteins, were significantly increased in SARS-CoV-2-infected children compared to the HC. Our findings suggest that immune response activation in the course of SARS-CoV-2 infection in children is directly correlated with clinical severity and, to a lesser extent, age.

show abstract

Circulating Adaptive Immune Cells Expressing the Gut Homing Marker α4β7 Integrin Are Decreased in COVID-19

Cited by 9 publications

References 47 publications

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

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

Prior SARS-CoV-2 infection enhances and reshapes spike protein–specific memory induced by vaccination

The Immunological Profile of SARS-CoV-2 Infection in Children Is Linked to Clinical Severity and Age

Contact Info

Product

Resources

About