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Mosole, S.

Publications and source records attributed to Mosole, S..

2 recordsLinked to original sources

Tattoo ink induces inflammation in the draining lymph node and impairs the immune response against a COVID-19 vaccine

Despite safety concerns regarding the toxicity of tattoo ink, no studies have reported the consequences of tattooing on the immune response. In this work, we have characterized the transport and accumulation of different tattoo inks in the lymphatic system using a murine model. Upon quick lymphatic drainage, we observed that macrophages mainly capture the ink in the lymph node (LN). An initial inflammatory reaction at local and systemic levels follows ink capture. Notably, the inflammatory process is maintained over time as we observed clear signs of inflammation in the draining LN two months following tattooing. In addition, the capture of ink by macrophages was associated with the induction of apoptosis in both human and murine models. Furthermore, the ink accumulated in the LN altered the immune response against a COVID-19 vaccine. We observed a reduced antibody response following vaccination with a mRNA-based SARS-CoV-2 vaccine, which was associated with a decreased expression of the Spike protein in macrophages in the draining LN. Considering the unstoppable trend of tattooing in the population, our results are crucial in informing the toxicology programs, policymakers, and the general public regarding the potential risk of the tattooing practice associated with an altered immune response.

immunology↗

Mitochondrial DNA released by senescent cells triggers immunosuppression in cancer

DNA is a potent damage-associated molecular pattern signaling that, once in the extracellular space, triggers the activation of the innate immune system. Here we find that senescent cells release mtDNA to both the cytosol and the extracellular space. In cells undergoing cellular senescence, the release of mtDNA precedes that of nuclear DNA resulting in the activation of the cGAS/STING pathway and establishment of cellular senescence. Intriguingly, by exploiting co-culture and in vivo cross-species experiments, we show that extracellular mtDNA released by senescent tumors cells is specifically captured by polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the tumor microenvironment (TME). Mechanistically we find that PMN-MDSCs uptake mtDNA to enhance their immunosuppressive ability. Pharmacological inhibition of mtDNA released from senescent tumor cells blocks the PMN-MDSCs immunosuppressive activity, improving the efficacy of therapy-induced senescence (TIS) in cancer. These results reveal the crucial role of mtDNA in initiating cellular senescence and immunosuppression independently of the SASP. Thus, targeting mtDNA release-mediated pathway may hold promise to reprogram the immune suppressive microenvironment in patients treated with chemotherapy.

cell biology↗