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Biology subjects

Bulut, O.

Publications and source records attributed to Bulut, O..

4 recordsLinked to original sources

Immune responses to human pathogens exposed to simulated Mars conditions

The identification of health risks associated with long-term crewed missions to Mars is critical for mission planning and crew safety. Human-associated pathogens can be part of the microbiome and are likely to be transported during these missions. This study examines the immunological responses of human immune cells stimulated with non-fastidious bacterial species that cause opportunistic infections, i.e. Klebsiella pneumoniae and Serratia marcescens, after exposure to simulated Martian conditions, including UV radiation, desiccation and atmospheric pressure. We observed that exposure of the bacteria to these conditions altered cytokine secretion, reactive oxygen species (ROS) production, and phagocytic activity in human peripheral blood mononuclear cells (PBMCs). Specifically, exposure to desiccation reduced cytokines and ROS production, indicating impaired innate immune recognition and stimulation. Notably, the altered immune response was partially restored when desiccated bacteria were regrown in standard media. Flow cytometry revealed decreased bacterial size and complexity of both species post-exposure. These findings indicate that Martian conditions induce bacterial morphological and physiological changes, which could impair immune recognition and response. Expanding these studies to in vivo models and a broader range of potentially pathogenic microorganisms is essential to estimate infection risks during Mars missions, which is vital for developing strategies to mitigate infection risks and maintain astronaut health during long-term space travel. ImportanceSince Yuri Gagarins 1961 flight, human space exploration has expanded, unintentionally transporting microorganisms, including pathogens, into space environments. Our previous studies demonstrated that opportunistic pathogens like Klebsiella pneumoniae and Serratia marcescens can survive simulated Mars conditions. With upcoming Mars missions, it is crucial to understand how such conditions influence these pathogens and their interaction with the human immune system. This research evaluates immune responses to bacteria pathogens exposed to Martian stressors such as UV radiation and desiccation, revealing significant changes of the immune responses to the exposed bacteria. These findings provide essential insights into the health risks that astronauts may face if infected with Mars-adapted pathogens. Understanding these interactions will help to develop preventive strategies and therapeutic measures, ensuring the safety and health of crew members during long-term missions. Ultimately, this work contributes to the broader objective of safe human exploration and colonization of Mars.

immunology↗

Fatty acid desaturation and lipoxygenase pathways support trained immunity

Infections and vaccinations can induce long-term enhanced responses of innate immune cells to heterologous stimuli, establishing a de facto innate immunological memory termed trained immunity. Monocytes exposed to the Bacillus Calmette-Guerin (BCG) vaccine, have a trained immunity phenotype, characterized by an increased biosynthesis of different lipid mediators (LMs) derived from long-chain polyunsaturated fatty acids (PUFAs). Pharmacological and genetic approaches showed that long-chain PUFA synthesis and lipoxygenase (LOX)-derived LMs are crucial for the BCG trained immunity responses of human monocytes. Furthermore, monocytes of healthy individuals vaccinated with BCG are enriched in 12-LOX products. The elucidation of the lipid metabolic pathways that promote innate immune memory contributes to our understanding of trained immunity and may help identify therapeutic tools and targets for the modulation of innate immune responses.

immunology↗

MMR vaccination induces a trained immunity program characterized by functional and metabolic reprogramming of γδ T cells

The measles, mumps and rubella (MMR) vaccine protects against all-cause mortality in children, but the immunological mechanisms mediating these effects are poorly known. We systematically investigated whether MMR can induce long-term functional changes in innate immune cells, a process termed trained immunity, that could at least partially mediate this heterologous protection. In a randomized placebo-controlled trial, 39 healthy adults received either the MMR vaccine or a placebo. By using single-cell RNA-sequencing, we found that MMR caused transcriptomic changes in CD14-positive monocytes and NK cells, but most profoundly in {gamma}{delta} T cells. Surprisingly, monocyte function was not altered by MMR vaccination. In contrast, the function of {gamma}{delta} T cells was significantly enhanced by MMR vaccination, with higher production of TNF and IFN{gamma}, as well as upregulation of cellular metabolic pathways. In conclusion, we describe a new trained immunity program characterized by modulation of {gamma}{delta} T cell function induced by MMR vaccination. One-sentence summaryMMR vaccination induces cellular and metabolic reprogramming in {gamma}{delta} T cells towards a more active phenotype.

immunology↗

The Immunological Factors Predisposing To Severe COVID-19 Are Already Present In Healthy Elderly And Men

BackgroundMale sex and old age are risk factors for COVID-19 severity, but the underlying causes are unknown. A possible explanation for this might be the differences in immunological profiles in males and the elderly before the infection. Given the seasonal profile of COVID-19, the seasonal response against SARS-CoV-2 could also be different in these groups. MethodsThe abundance of circulating proteins and immune populations associated with severe COVID-19 was analyzed in 2 healthy cohorts. PBMCs of female, male, young, and old subjects in different seasons of the year were stimulated with heat-inactivated SARS-CoV-2. ResultSeveral T cell subsets, which are known to be depleted in severe COVID-19 patients, were intrinsically less abundant in men and older individuals. Plasma proteins increasing with disease severity, including HGF, IL-8, and MCP-1, were more abundant in the elderly and males. The elderly produced significantly more IL-1RA and had a dysregulated IFN{gamma} response with lower production in the summer compared with young individuals. ConclusionsThe immune characteristics of severe COVID-19, described by a differential abundance of immune cells and circulating inflammatory proteins, are intrinsically present in healthy men and the elderly. This might explain the susceptibility of men and the elderly to SARS-CoV-2 infection. SummaryImmunological profile of severe COVID-19, characterized by altered immune cell populations and inflammatory plasma proteins is intrinsically present in healthy men and the elderly. Different age and sex groups show distinct seasonal responses to SARS-CoV-2.

immunology↗