Search

Confirmed SARS-coronavirus-2 infection with gastrointestinal symptoms and changes in microbiota associated with coronavirus disease 2019 (COVID-19) severity have been previously reported, but the disease impact on the architecture and cellularity of ileal Peyer’s patches (PP) remains unknown. Here we analysed post-mortem tissues from throughout the gastrointestinal (GI) tract of patients who died with COVID-19. When virus was detected by PCR in the GI tract, immunohistochemistry identified virus in epithelium and lamina propria macrophages, but not in lymphoid tissues. Immunohistochemistry and imaging mass cytometry (IMC) analysis of ileal PP revealed depletion of germinal centres (GC), disruption of B cell/T cell zonation and decreased potential B and T cell interaction and lower nuclear density in COVID-19 patients. This occurred independent of the local viral levels. The changes in PP demonstrate that the ability to mount an intestinal immune response is compromised in severe COVID-19, which could contribute to observed dysbiosis.

Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. Atherosclerosis is directly associated with CVD and is characterized by slow progressing inflammation which results in the deposition and accumulation of lipids beneath the endothelial layer in conductance and resistance arteries. Both chronic inflammation and disease progression have been associated with several risk factors, including but not limited to smoking, obesity, diabetes, genetic predisposition, hyperlipidemia, and hypertension. Currently, despite increasing incidence and significant expense on the healthcare system in both western and developing countries, there is no curative therapy for atherosclerosis. Instead patients rely on surgical intervention to avoid or revert vessel occlusion, and pharmacological management of the aforementioned risk factors. However, neither of these approaches completely resolve the underlying inflammatory environment which perpetuates the disease, nor do they result in plaque regression. As such, immunomodulation could provide a novel therapeutic option for atherosclerosis; shifting the balance from proatherogenic to athero-protective. Indeed, regulatory T-cells (Tregs), which constitute 5-10% of all CD4 + T lymphocytes in the peripheral blood, have been shown to be athero-protective and could function as new targets in both CVD and atherosclerosis. This review aims to give a comprehensive overview about the roles of Tregs in CVD, focusing on atherosclerosis.

The ST2 receptor is a member of the Toll/IL-1R superfamily and interleukin-33 (IL-33) is its agonist. Recently, it has been demonstrated that IL-33/ST2 axis plays key roles in inflammation and immune mediated diseases. Here, we investigated the effect of ST2 deficiency in Staphylococcus aureus-induced septic arthritis physiopathology. Synovial fluid samples from septic arthritis and osteoarthritis individuals were assessed regarding IL-33 and soluble (s) ST2 levels. The IL-33 levels in samples from synovial fluid were significantly increased, whereas no sST2 levels were detected in patients with septic arthritis when compared with osteoarthritis individuals. The intra-articular injection of 1 × 107 colony-forming unity/10 μl of S. aureus American Type Culture Collection 6538 in wild-type (WT) mice induced IL-33 and sST2 production with a profile resembling the observation in the synovial fluid of septic arthritis patients. Data using WT, and ST2 deficient (−/−) and interferon-γ (IFN-γ)−/− mice showed that ST2 deficiency shifts the immune balance toward a type 1 immune response that contributes to eliminating the infection due to enhanced microbicide effect via NO production by neutrophils and macrophages. In fact, the treatment of ST2−/− bone marrow-derived macrophage cells with anti-IFN-γ abrogates the beneficial phenotype in the absence of ST2, which confirms that ST2 deficiency leads to IFN-γ expression and boosts the bacterial killing activity of macrophages against S. aureus. In agreement, WT cells achieved similar immune response to ST2 deficiency by IFN-γ treatment. The present results unveil a previously unrecognized beneficial effect of ST2 deficiency in S. aureus-induced septic arthritis.