IL-7 in SARS-CoV-2 Infection and as a Potential Vaccine Adjuvant

Bekele, Yonas; Sui, Yongjun; Berzofsky, Jay A.

doi:10.3389/fimmu.2021.737406

Cited by 22 publications

(18 citation statements)

References 45 publications

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“…Of note, among genes selectively modulated in cytotoxic monocyte subpopulations but not in the others, we identified the IL-7 receptor ( IL-7R ) ( Figure 5F ). Since the recombinant human IL-7 (rhIL-7) has been evaluated as promising vaccine adjuvant against SARS-Cov-2 ( 59 ), we asked whether IL-7R is expressed by all monocytes and upregulated only in the cytotoxic monocytes from moderate patients or if the receptor is selectively expressed by this subpopulation. Interestingly, while other subsets showed low levels of IL-7R , both cMo and ncMo cytotoxic resulted as the most expressing cells ( Figures 5G ).…”

Section: Resultsmentioning

confidence: 99%

Distinct responses of newly identified monocyte subsets to advanced gastrointestinal cancer and COVID-19

et al. 2022

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Monocytes are critical cells of the immune system but their role as effectors is relatively poorly understood, as they have long been considered only as precursors of tissue macrophages or dendritic cells. Moreover, it is known that this cell type is heterogeneous, but our understanding of this aspect is limited to the broad classification in classical/intermediate/non-classical monocytes, commonly based on their expression of only two markers, i.e. CD14 and CD16. We deeply dissected the heterogeneity of human circulating monocytes in healthy donors by transcriptomic analysis at single-cell level and identified 9 distinct monocyte populations characterized each by a profile suggestive of specialized functions. The classical monocyte subset in fact included five distinct populations, each enriched for transcriptomic gene sets related to either inflammatory, neutrophil-like, interferon-related, and platelet-related pathways. Non-classical monocytes included two distinct populations, one of which marked specifically by elevated expression levels of complement components. Intermediate monocytes were not further divided in our analysis and were characterized by high levels of human leukocyte antigen (HLA) genes. Finally, we identified one cluster included in both classical and non-classical monocytes, characterized by a strong cytotoxic signature. These findings provided the rationale to exploit the relevance of newly identified monocyte populations in disease evolution. A machine learning approach was developed and applied to two single-cell transcriptome public datasets, from gastrointestinal cancer and Coronavirus disease 2019 (COVID-19) patients. The dissection of these datasets through our classification revealed that patients with advanced cancers showed a selective increase in monocytes enriched in platelet-related pathways. Of note, the signature associated with this population correlated with worse prognosis in gastric cancer patients. Conversely, after immunotherapy, the most activated population was composed of interferon-related monocytes, consistent with an upregulation in interferon-related genes in responder patients compared to non-responders. In COVID-19 patients we confirmed a global activated phenotype of the entire monocyte compartment, but our classification revealed that only cytotoxic monocytes are expanded during the disease progression. Collectively, this study unravels an unexpected complexity among human circulating monocytes and highlights the existence of specialized populations differently engaged depending on the pathological context.

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Section: Resultsmentioning

confidence: 99%

Distinct responses of newly identified monocyte subsets to advanced gastrointestinal cancer and COVID-19

et al. 2022

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“…These R&D efforts are yet to deliver convincing evidence of their effectiveness. However, anti-PD1/PDL1 and IL-7 therapeutics have shown signs of usefulness and efficacy during clinical trials [ 132 , 133 ]. Thus, similar strategies would be effective in treating SARS-CoV-2 infected patients.…”

Section: Immune-boosting Strategiesmentioning

confidence: 99%

“…Thus, similar strategies would be effective in treating SARS-CoV-2 infected patients. Bekele et al further revealed that IL-7 could aid to protect T cells from death, promote the proliferation of T cells, and support reversing lymphopenia in SARS-CoV-2 infected patients suffering from sepsis [ 133 ].…”

Section: Immune-boosting Strategiesmentioning

confidence: 99%

Significance of Immune Status of SARS-CoV-2 Infected Patients in Determining the Efficacy of Therapeutic Interventions

Saratale

Shin

Shinde

et al. 2022

JPM

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Coronavirus disease 2019 (COVID-19) is now being investigated for its distinctive patterns in the course of disease development which can be indicated with miscellaneous immune responses in infected individuals. Besides this series of investigations on the pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significant fundamental immunological and physiological processes are indispensable to address clinical markers of COVID-19 disease and essential to identify or design effective therapeutics. Recent developments in the literature suggest that deficiency of type I interferon (IFN) in serum samples can be used to represent a severe progression of COVID-19 disease and can be used as the basis to develop combined immunotherapeutic strategies. Precise control over inflammatory response is a significant aspect of targeting viral infections. This account presents a brief review of the pathophysiological characteristics of the SARS-CoV-2 virus and the understanding of the immune status of infected patients. We further discuss the immune system’s interaction with the SARS-CoV-2 virus and their subsequent involvement of dysfunctional immune responses during the progression of the disease. Finally, we highlight some of the implications of the different approaches applicable in developing promising therapeutic interventions that redirect immunoregulation and viral infection.

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“…There are contradictory interpretations regarding the role of IL-7; in fact, evidence supports a beneficial role in COVID-19 as demonstrated in a small group of critically ill patients where the administration of IL-7 induced an increase in lymphocyte count without causing either lung damage or evident hyperinflammation [ 15 ]. A role for this cytokine as vaccine adjuvant has also been proposed [ 16 ]. Nevertheless, the augmentation of IL-7 above physiological levels may have a detrimental role disrupting the immunobalance [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Cytokine and Chemokine Retention Profile in COVID-19 Patients with Chronic Kidney Disease

Ciceri

Bono

Magagnoli

et al. 2022

Toxins

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Chronic kidney disease (CKD) patients are more susceptible to infections compared to the general population. SARS-CoV-2 virus pathology is characterized by a cytokine storm responsible for the systemic inflammation typical of the COVID-19 disease. Since CKD patients have a reduced renal clearance, we decided to investigate whether they accumulate harmful mediators during the COVID-19 disease. We conducted a retrospective study on 77 COVID-19 hospitalized subjects in the acute phase of the illness. Thirteen different cytokines were assessed in plasma collected upon hospitalization. The patients were divided into three groups according to their estimated glomerular filtration rate, eGFR < 30 (n = 23), 30 < eGFR < 60 (n = 33), eGFR > 60 mL/min (n = 21). We found that Tumor Necrosis Factor α and its receptors I and II, Interleukin-7, Leukemia Inhibitory Factor, FAS receptor, Chitinase 3-like I, and the Vascular Endothelial Growth Factor showed an increased accumulation that negatively correlate with eGFR. Moreover, non-survivor patients with an impaired kidney function have significantly more elevated levels of the same mediators. In conclusion, there is a tendency in COVID-19 ESRD patients to accumulate harmful cytokines. The accumulation seems to associate with mortality outcomes and may be due to reduced clearance but also to increased biosynthesis in most severe cases.

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IL-7 in SARS-CoV-2 Infection and as a Potential Vaccine Adjuvant

Cited by 22 publications

References 45 publications

Distinct responses of newly identified monocyte subsets to advanced gastrointestinal cancer and COVID-19

Distinct responses of newly identified monocyte subsets to advanced gastrointestinal cancer and COVID-19

Significance of Immune Status of SARS-CoV-2 Infected Patients in Determining the Efficacy of Therapeutic Interventions

Cytokine and Chemokine Retention Profile in COVID-19 Patients with Chronic Kidney Disease

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