Biology subjects

Vitalle, J.

Publications and source records attributed to Vitalle, J..

4 recordsLinked to original sources

bioRxiv2021

Deciphering the quality of SARS-CoV-2 specific T-cell response associated with disease severity, immune memory and heterologous response

SARS-CoV-2 specific T-cell response has been associated with disease severity, immune memory and heterologous response to endemic coronaviruses. However, an integrative approach combining a comprehensive analysis of the quality of SARS-CoV-2 specific T-cell response with antibody levels in these three scenarios is needed. In the present study we found that, in acute infection, while mild disease was associated with high T-cell polyfunctionality biased to IL-2 production and inversely correlated with anti-S IgG levels, combinations only including IFN-{gamma} with absence of perforin production predominated in severe disease. Seven months after infection, both non-hospitalized and previously hospitalized patients presented robust anti-S IgG levels and SARS-CoV-2 specific T-cell response. In addition, only previously hospitalized patients showed a T-cell exhaustion profile. Finally, combinations including IL-2 in response to S protein of endemic coronaviruses, were the ones associated with SARS-CoV-2 S-specific T-cell response in pre-COVID-19 healthy donors samples. These results have implications for protective immunity against SARS-CoV-2 and recurrent COVID-19 and may help for the design of new prototypes and boosting vaccine strategies.

immunology↗

bioRxiv2021

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-). In COVID-19 there is a deficit in DC numbers and IFN- production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and non-hospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers as CD86 and CD4 were only restored in previously non-hospitalized patients while integrin {beta}7 and indoleamine 2,3- dyoxigenase (IDO) no restoration was observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19.

immunology↗

bioRxiv2020

Human cytokine-induced memory-like NK cells preserve increased glycolysis but the glycolytic-dependence of their effector functions differ between stimuli

Natural Killer (NK) cells acquire memory-like properties following a brief stimulation with IL-12, IL-15 and IL-18. These IL-12/15/18-stimulated NK cells, also known as cytokine-induced memory-like (CIML) NK cells, have been revealed as a powerful tool in cancer immunotherapy due to their persistence in the host and their increased effector functions. Several studies have shown that NK cells modulate their metabolism in response to cytokine-stimulation and other stimuli, suggesting that there is a link between metabolism and cellular functions. In this paper, we have analyzed metabolic changes associated to IL-12/15/18-stimulation and the relevance of glycolytic pathway for NK cell effector functions. We have found that CIML NK cells are able to retain increased glycolytic machinery seven days after cytokine withdrawal. Furthermore, we found that glycolytic inhibition with 2-DG is stimuli-dependent and that differently affects to distinct effector functions. These findings may have implications in the design of NK cell-based cancer immunotherapies.

immunology↗

bioRxiv2020

A NKp80-based identification strategy reveals that CD56neg NK cells are not completely dysfunctional in health and disease.

Natural killer (NK) cells are usually identified by the absence of other lineage markers, due to the lack of a cell surface specific marker. CD56neg NK cells, classically identified as CD56negCD16+ are known to be expanded in some pathological conditions. However, studies on CD56neg NK cells had revealed different results regarding the phenotype and functionality of these cells. This could be due to, among others, the unstable expression of CD16, which hinders CD56neg NK cells identification. Hence, we aim to determine an alternative surface marker to CD16 to better identify CD56neg NK cells. Using multiparametric flow cytometry, we have found that NKp80 is a good alternative to CD16 not only in healthy donors but also in HIV-1 infected subjects and multiple myeloma patients. Furthermore, we found differences between the functionality of CD56negNKp80+ and CD56negCD16+ NK cells both in healthy donors and patients, suggesting that the effector functions of CD56neg NK cells are not as diminished as previously thought. We proposed NKp80 as a noteworthy marker to identify and accurately re-characterize human CD56neg NK cells.

immunology↗