Unbiased immunome characterisation correlates with COVID-19 mRNA vaccine failure in immunocompromised adults.

Introduction: Coronavirus disease 2019 (COVID-19) affects the population unequally, with a greater impact on older and immunosuppressed people.

Methods: Hence, we performed a prospective experimental cohort study to characterise the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in immune-compromised patients (older adults and oncohaematologic patients), compared with healthy counterparts, based on deep characterisation of the circulating immune cell subsets.

Results And Discussion: While acquired humoral and cellular memory did not predict subsequent infection 18 months after full vaccination, spectral and computational cytometry revealed several subsets within the CD8 T-cells, B-cells, natural killer (NK) cells, monocytes and TEMRA Tγδ cells that were differentially expressed in individuals who were subsequently infected and not infected not just following immunisation, but also prior to vaccination.

Innate IRE1α-XBP1 activation by viral single-stranded RNA and its influence on lung cytokine production during SARS-CoV-2 pneumonia.

The utilization of host-cell machinery during SARS-CoV-2 infection can overwhelm the protein-folding capacity of the endoplasmic reticulum and activate the unfolded protein response (UPR). The IRE1α-XBP1 arm of the UPR could also be activated by viral RNA via Toll-like receptors. Based on these premises, a study to gain insight into the pathogenesis of COVID-19 disease was conducted using nasopharyngeal exudates and bronchioloalveolar aspirates.

Development of a novel in vitro model to study the modulatory role of the respiratory complex I in macrophage effector functions.

Increasing evidence demonstrate that the electron transfer chain plays a critical role in controlling the effector functions of macrophages. In this work, we have generated a Ndufs4-/- murine macrophage cell lines. The Ndufs4 gene, which encodes a supernumerary subunit of complex I, is a mutational hotspot in Leigh syndrome patients.

The mitochondrial succinate dehydrogenase complex controls the STAT3-IL-10 pathway in inflammatory macrophages.

The functions of macrophages are tightly regulated by their metabolic state. However, the role of the mitochondrial electron transport chain (ETC) in macrophage functions remains understudied. Here, we provide evidence that the succinate dehydrogenase (SDH)/complex II (CII) is required for respiration and plays a role in controlling effector responses in macrophages.