Recently, the increased prevalence of chronic civilization diseases triggered by environmental pollution has been observed. In this context, the role of air pollution in the pathogenesis of autoimmune and/or inflammatory disorders is poorly elucidated. Here, we asked whether seasonal changes in the air quality of the city of Cracow affect the polarization of T cell subsets in healthy donors (HD) and patients with rheumatoid arthritis (RA), multiple sclerosis (MS), and atherosclerosis (AS). Peripheral blood mononuclear cells (PBMCs) from HD and patients were exposed in vitro to particulate matter isolated from the air of Cracow (PM CRC). Blood samples were collected in two seasons (winter and summer), with differences in air concentration of particulate matter of 10 μm (PM10) (below or above a daily limit of 50 µg/m3). The obtained data showed a significantly elevated frequency of CD4+ lymphocytes specific for IFN-γ and IL-17A after the exposure of PBMCs to PM CRC. This was observed for all patients’ groups and HD. In the case of patients, this effect was dependent on the seasonal concentration of PM in the air, paradoxically being less pronounced in the season with a higher concentration of air pollution. These observations may suggest the role of air pollution on the course of inflammatory and autoimmune disorders.

IntroductionNatural killer (NK) cells plays a pivotal role in the control of viral infections, and their function depend on the balance between their activating and inhibitory receptors. The immune dysregulation observed in COVID-19 patients was previously associated with downregulation of NK cell numbers and function, yet the mechanism of inhibition of NK cell functions and the interplay between infected cells and NK cells remain largely unknown. MethodsIn this study we show that SARS-CoV-2 infection of airway epithelial cells can directly influence NK cell phenotype and functions in the infection microenvironment. NK cells were co-cultured with SARS-CoV-2 infected epithelial cells, in a direct contact with A549ACE2/TMPRSS2 cell line or in a microenvironment of the infection in a 3D ex vivo human airway epithelium (HAE) model and NK cell surface expression of a set of most important receptors (CD16, NKG2D, NKp46, DNAM-1, NKG2C, CD161, NKG2A, TIM-3, TIGIT, and PD-1) was analyzed. ResultsWe observed a selective, in both utilized experimental models, significant downregulation the proportion of CD161 (NKR-P1A or KLRB1) expressing NK cells, and its expression level, which was followed by a significant impairment of NK cells cytotoxicity level against K562 cells. What is more, we confirmed that SARS-CoV-2 infection upregulates the expression of the ligand for CD161 receptor, lectin-like transcript 1 (LLT1, CLEC2D or OCIL), on infected epithelial cells. LLT1 protein can be also detected not only in supernatants of SARS-CoV-2 infected A549ACE2/TMPRSS2 cells and HAE basolateral medium, but also in serum of COVID-19 patients. Finally, we proved that soluble LLT1 protein treatment of NK cells significantly reduces i) the proportion of CD161+ NK cells, ii) the ability of NK cells to control SARS-CoV-2 infection in A549ACE2/TMPRSS2 cells and iii) the production of granzyme B by NK cells and their cytotoxicity capacity, yet not degranulation level. ConclusionWe propose a novel mechanism of SARS-CoV-2 inhibition of NK cell functions via activation of the LLT1-CD161 axis.

The first line of antiviral immune response in the lungs is secured by the innate immunity. Several cell types take part in this process, but airway macrophages (AMs) are among the most relevant ones. The AMs can phagocyte infected cells and activate the immune response through antigen presentation and cytokine release. However, the precise role of macrophages in the course of SARS-CoV-2 infection is still largely unknown. In this study, we aimed to evaluate the role of AMs during the SARS-CoV-2 infection using a co-culture of fully differentiated primary human airway epithelium (HAE) and human monocyte-derived macrophages (hMDMs). Our results confirmed abortive SARS-CoV-2 infection in hMDMs, and their inability to transfer the virus to epithelial cells. However, we demonstrated a striking delay in viral replication in the HAEs when hMDMs were added apically after the epithelial infection, but not when added before the inoculation or on the basolateral side of the culture. Moreover, SARS-CoV-2 inhibition by hMDMs seems to be driven by cell-to-cell contact and not by cytokine production. Together, our results show, for the first time, that the recruitment of macrophages may play an important role during the SARS-CoV-2 infection, limiting the virus replication and its spread.

Nano-sized radiosensitizers can be used to increase the effectiveness of radiation-based anticancer therapies. In this study, bimetallic, ⁓30 nm palladium-platinum nanoparticles (PdPt NPs) with different nanostructures (random nano-alloy NPs and ordered core-shell NPs) were prepared. Scanning transmission electron microscopy (STEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDS), zeta potential measurements, and nanoparticle tracking analysis (NTA) were used to provide the physicochemical characteristics of PdPt NPs. Then, PdPt NPs were added to the cultures of colon cancer cells and normal colon epithelium cells in individually established non-toxic concentrations and irradiated with the non-harmful dose of X-rays/protons. Cell viability before and after PdPt NPs-(non) assisted X-ray/proton irradiation was evaluated by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Flow cytometry was used to assess cell apoptosis. The results showed that PdPt NPs significantly enhanced the effect of irradiation on cancer cells. It was noticed that nano-alloy PdPt NPs possess better radiosensitizing properties compared to PtPd core-shell NPs, and the combined effect against cancer cells was c.a. 10% stronger for X-ray than for proton irradiation. Thus, the radio-enhancing features of differently structured PdPt NPs indicate their potential application for the improvement of the effectiveness of radiation-based anticancer therapies.

Despite the general awareness of the need to reduce air pollution, the efforts were undertaken in Poland to eliminate the pollutants and their harmful effect on human health seem to be insufficient. Moreover, the latest data indicate that the city of Krakow is at the forefront of the most polluted cities worldwide. Hence, in this report, we investigated the impact of particulate matter isolated from the air of Krakow (PM KRK) on the gene expression profile of peripheral blood mononuclear cells (PBMCs) in healthy donors (HD) and patients with atherosclerosis (AS), rheumatoid arthritis (RA) and multiple sclerosis (MS), after in vitro exposure. Blood samples were collected in two seasons, differing in the concentration of PM in the air (below or above a daily limit of 50 µg/m3 for PM 10). Data show that PBMCs exposed in vitro to PM KRK upregulated the expression of genes involved, among others, in pro-inflammatory response, cell motility, and regulation of cell metabolism. The transcriptional effects were observed predominantly in the group of patients with AS and MS. The observed changes seem to be dependent on the seasonal concentration of PM in the air of Krakow and may suggest their important role in the progression of AS, MS, and RA in the residents of Krakow.

The first line of antiviral immune response in the lungs is secured by the innate immunity. Several cell types take part in this process, but airway macrophages (AMs) are among the most relevant ones. The AMs can phagocyte infected cells and activate the immune response through antigen presentation and cytokine release. However, the precise role of macrophages in the course of SARS-CoV-2 infection is still largely unknown. In this study, we aimed to evaluate the role of AMs during the SARS-CoV-2 infection using a co-culture of fully differentiated primary human airway epithelium (HAE) and human monocyte-derived macrophages (hMDMs). Our results confirmed abortive SARS-CoV-2 infection in hMDMs, and their inability to transfer the virus to epithelial cells. However, we demonstrated a striking inhibition of viral replication in the HAEs when hMDMs were added apically after the epithelial infection, but not when added before the inoculation or on the basolateral side of the culture. Moreover, SARS-CoV-2 inhibition by hMDMs seems to be driven by cell-to-cell contact and not by the cytokine production. Together, our results show, for the first time, that recruitment of macrophages may play an important role during the SARS-CoV-2 infection, limiting the virus replication and its spread.