Obstructive sleep apnea syndrome (OSAS) represents a substantial disease of recurrent sleep fragmentation, leading to intermittent hypoxia and subsequent diseases such as cardiovascular, metabolic, or cognitive dysfunctions. In addition, OSAS is considered as low-grade systemic inflammation, which is associated with a higher incidence of cancer, severity of infections, and an overall immune dysregulation. This research project aims to comprehensively investigate the interplay of wholesome sleep and the immune functions of circulating monocytes and T cells in OSAS patients, which are known to be affected by oxidative stress. We studied the distribution of the CD14/CD16 characterized monocyte subsets in peripheral blood as well as their PD-L1 expression and complex formation with T cells. Furthermore, a detailed analysis of T cell subsets with regard to their PD-1 and PD-L1 expression was performed. Data revealed a decrease of classical monocytes accompanied by an increase of both CD16 + monocyte subsets in OSAS patients that was positively correlated with the body mass index. OSAS patients revealed an increased PD-1 and PD-L1 expression in T cells and monocytes, respectively, which was linked to the severity of monocyte subset alterations. The complex formation of monocytes and T cells was also elevated in OSAS patients, which indicates a deregulated PD-1/PD-L1 cross-talk between these cells. Our data show for the first time, to our knowledge, massive alterations of peripheral monocyte subsets in response to OSAS and its accompanying phenomena.

Platelets (PLT) are the second most abundant cell type in human blood and exert various immune-regulatory functions under both physiological and pathological conditions. In fact, immune cell regulation via platelets has been demonstrated in several studies within the past decade. However, the exact mechanisms behind T cell regulation remain poorly understood. We questioned whether the formation of aggregates of platelets and T cells has an impact on T-cell functions. In the present study, we stimulated PBMC cultures with anti-CD3 and anti-CD28 mABs and cultured them at a PLT: PBMC ratio of 1:1 or 100:1. After 24, 48, and 72 h, PD-1, PD-L1 expression, and proliferation were analyzed on T cells using flow cytometry. Cytokine production was measured in PHA stimulated CD4 cells after 6 h. We found a significant platelet-mediated decrease in PD-1 and PD-L1 expression, proliferation, as well as IFN-γ and TNF-α production. Perturbations also at least partially remained after spatial separation of PLTs from PBMCs in Transwell-assays. T cell-platelet aggregates showed similar levels of activation markers, proliferation, and secreted cytokines as their non-complexed counterparts. Results indicate a platelet mediated regulation of T cells via direct and indirect contact, but only mediocre effects of the complex formation itself.

Obstructive sleep apnea (OSA) is characterized by nocturnal breathing intermissions resulting in oxidative stress and eventually, a low-grade systemic inflammation. The study aimed to investigate the impact of positive airway pressure (PAP) therapy on the inflammatory milieu as measured by monocyte and T cell phenotypic alterations. Participants were assessed for their OSA severity before PAP therapy and about six months later, including patient-reported outcome and therapy usage by telemetry readout. The distributions of the CD14/CD16-characterized monocyte subsets as well as the CD4/CD8-characterized effector T cell subsets with regard to their PD-1 and PD-L1 expression were analyzed by flow cytometry from blood samples. Data of 25 patients revealed a significant reconstitution of the monocyte subset distribution and a decrease in PD-L1 expression on pan-monocytes and CD8+ T cells without an association to initial AHI and overweight. The PD-1 expression was still increased on T cell subsets, especially on CD4+ TH17/22 cells. We conclude that PAP therapy might have a rapid effect on the monocyte phenotype and overall PD-L1 expression levels. However, T cell immune alterations especially on TH17/22 cells persist longer, indicating an ongoing disturbance of the adaptive immune system.

Superparamagnetic iron oxide nanoparticles (SPIONs) are currently under examination for magnetic particle imaging, which represents a radiation free technology for three-dimensional imaging with high sensitivity, resolution and imaging speed. SPIONs are rapidly taken up by monocytes and other phagocytes which carry them to the site of inflammation. Therefore, the SPION biocompatibility is an essential parameter for a widespread MPI usage. Many improvements are expected from SPION development and its applications for cell visualization, but the impact of MPI optimized dextran coated SPIONs on the cellular characteristics of monocytic cells has been poorly studied up to now. THP-1 monocytes, monocyte-derived macrophages (MDM) as well as peripheral blood monocytes were incubated with MPI-optimized dextran-coated SPIONs of a size between 83.5 and 86 nm. SPION uptake was measured by FITC fluorescence of labeled SPIONs and Prussian blue staining. The activation of monocytes and MDMs was evaluated by CD14, CD11b and CD86 in flow cytometry. The secretion of IL-1β, and IL-10 was analyzed in supernatants. SPIONs were rapidly taken up by monocytes and monocyte-derived macrophages while no decrease in cell viability was observed. Expression patterns of CD11b, CD14, and CD86 were not affected in THP-1 monocytes and MDMs. Monocyte differentiation in macrophages was hindered during SPION uptake. THP-1 monocytes as well as monocyte-derived macrophages showed significantly increased IL-1β and decreased IL-10 secretion by tendency after SPION treatment. Dextran-coated SPIONs showed a low cytotoxicity on monocytes but exert undesirable inflammatory side effects that have to be considered for imaging applications.

This paper provides a brief historical background of saline nasal irrigation (SNI), main modes of SARS-COV-2 transmission and entry, and anti-infective properties of saline. It reviews the protective evidence associated with SNI and gargling against viral upper respiratory tract infection (URTI). SARS-CoV-2 presents as an URTI transmitted mainly via respiratory droplets and aerosols to the oro-nasal mucosa and indirectly after touching these entry sites from contaminated fomites. It can potentially be transmitted from the conjunctival mucosa to the nasal mucosa or from resuspension and inhalation from the facial area around the nose. SNI has antiviral, anti-inflammatory and mucociliary restorative properties. Numerous randomized controlled trials have reported that SNI, with and without gargling, prevents and treats viral URTI. Based on biological rationale and anecdotal evidence we suggest a protocol: Soap and Water to the Hands and Face-Eye Rinse Nasal Irrigation and Gargling with Saline (SWHF-ERNIGS) may limit the transmission SARS-CoV-2, and prevent and treat COVID-19 infection. Clinical considerations of the protocol are presented. The protocol is safe, straightforward and can be easily performed by healthcare workers and the general public; it uses readily available salt, water and soap. Formal studies of effectiveness and application of the protocol are warranted.