Early in our scientific careers, we learn about the many advantages of working abroad to upskill and expand our research horizons. Born and raised in Montevideo, Uruguay, I always had a clear passion for science and foreign cultures, nurtured by my family. I had been preparing for a career in science and living abroad all my life, so when the time came, I felt ready. Looking back a decade, I realize how little I knew about the challenges ahead and how much I learned ‘on the go’. The significant personal and professional transition of continuing your career abroad is exciting but also challenging, especially for those coming from countries with limited budgets and more flexible research environments. The exposure to state-of-the-art technologies, new ways of thinking, and working within unfamiliar regulatory frameworks without your usual support network, at times can feel overwhelming. Like navigating uncharted waters, succeeding abroad requires not only planning but resilience and adaptability. Embracing uncertainty and learning to slow down when needed can be invaluable. By sharing my experiences, I hope to offer useful insights for those preparing to emigrate or establish themselves elsewhere.

not-yet-known not-yet-known not-yet-known unknown Amy is a Research Advisor for the Ovarian Cancer Research Foundation (OCRF) and an Honorary Research Associate at the Hudson Institute of Medical Research in Melbourne, Australia. She was previously a postdoctoral researcher at the Hudson Institute focusing on ovarian leader cells and how they drive metastasis and chemoresistance. This article explores her journey from ovarian cancer researcher to a research advisory role in the not-for-profit sector. Driven by a deep love for science and a desire to make an impact, she navigated the challenges of the research environment and the uncertainties of career transition. Along the way, Amy discovered the importance of transferable skills, mentorship, and creativity, which have all played crucial roles in shaping her career. With a future full of possibilities, Amy’s commitment to making a difference continues to inspire and guide her.

Phagocytosis is an immunological characteristic that assists the host immune defense in recognizing and responding effectively to foreign pathogenic molecules and other self-antigens. Understanding the phagocytic activities against malaria infection in the context of Plasmodium falciparum infection which represents a major public health concern in many countries is crucial for developing effective interventions to prevent and control malaria, and improving the overall notion about the importance of this mechanism in the protective immune response. Previous studies have shown that various factors such as the type of phagocyte cells, plasma molecules, and the evasion of tactics by Plasmodium falciparum pathogens influence the phagocytic process. However, the mechanisms underlying phagocytic activity during Plasmodium falciparum infection are still not fully understood. This review aims to provide a comprehensive insight into the current state of knowledge on phagocytic activities in Plasmodium falciparum infection, highlighting the significant involvement of different active phagocyte cells, influences on phagocytosis, and giving perspective on the therapeutic approach and implications of this immunological activity in malaria infection clearance.

This report was produced by an Expert Working Group consisting of UK-based researchers with specialist knowledge of the use of animal models of bone marrow ablation and reconstitution. It aims to facilitate the implementation of the Three Rs (Replacement, Reduction and Refinement), with an emphasis on refinement. Bone marrow ablation and reconstitution procedures are done for a number of different purposes and conducted primarily in mice. These procedures can induce significant suffering, classified as ‘severe’, Category E or Category D/E under European, US and Canadian legislation respectively. Specific animal welfare issues were identified and discussed, and practical measures proposed, with the aim of reducing animal use and suffering.

We newly developed a hybrid protein, tentatively named human MIKO-1 (hM1), based on the amino acid sequences of human S100A8 (hS100A8) and hS100A9. Human macrophage-like cells (hMΦ), which were differentiated from THP-1 cells by phorbol 12-myristate 13-acetate, were used to investigate the immune function of hM1 and its dynamic mobility in cells. Western blotting was conducted to detect hM1 in the cytoplasm and nucleus of hMΦ. A polymerase chain reaction (PCR) and quantitative PCR were performed to examine changes in the mRNA levels of proinflammatory cytokines in hMΦ. Fluorescent immunochemical staining was conducted to microscopically observe the intracellular behavior of hM1 in hMΦ, together with hS100A8 and/or hS100A9. Microscopic observations showed that hM1 rapidly bound to activated hMΦ and immediately migrated even inside the nucleus of these cells. The intracellular localization of hM1 in hMΦ almost coincided with that of hS100A8, suggesting the close involvement of hS100A8 in the intracellular behavior of hM1 in hMΦ. The mRNA expression of each proinflammatory cytokine was significantly suppressed in hMΦ preliminarily treated with hM1 despite a subsequent stimulation with lipopolysaccharide. Significant decreases in the mRNA levels of proinflammatory cytokines in hMΦ strongly suggest the potential of hM1 as a negative regulator of inflammation. hM1 may land on a special site on the DNA chain, such as the NF-κB motif, in the nucleus to directly inhibit the mRNA expression of proinflammatory cytokines. In conclusion, hM1 is a prominent player that significantly attenuates the cytokine storm caused by excessively activated hMΦ.

The Gastroenterology Immunology Neuroscience (GIN) Discovery Program represents a new model for research that overcomes the limitations imposed by traditional ‘research silos’ in medical science. By adopting a cross-disciplinary, highly-integrated approach, the GIN Program unites the fields of gastroenterology, immunology, and neuroscience to comprehensively address chronic health challenges. This initiative not only bridges the gaps between basic science, clinical research, and patient care but also emphasises the importance of diversity in ideas, perspectives, and approaches when fostering innovation. The program’s organic, bottom-up growth strategy has facilitated the formation of a vibrant, interdisciplinary community, captivating attention from both national and international institutions. With a vision to create effective therapeutic solutions and pioneer advancements in gut-immune-brain axis research, the GIN Program exemplifies the power of interdisciplinary collaboration. This innovative commitment to change the landscape of medical research aims to inspire similar models that prioritise open communication, mutual respect, and a commitment to groundbreaking science.

CD8+ T cells recognising their cognate antigen are typically recruited as a polyclonal population consisting of multiple clonotypes with varying T-cell receptor (TCR) affinity to the target peptide-MHC (pMHC) complex. Advances in single-cell sequencing have increased accessibility towards identifying TCRs with matched antigens. Here we present the discovery of a monoclonal CD8+ T cell population with specificity for a hepatitis C virus (HCV)-derived HLA class I epitope (HLA-B*07:02 GPRLGVRAT) which was isolated directly ex vivo from an individual with an episode of acutely resolved HCV infection. This population was absent prior to infection and underwent expansion and stable maintenance for at least two years after infection as measured by HLA-multimer staining. Furthermore, the monoclonal clonotype was characterised by an unusually long dissociation time (half-life = 794 seconds and koff = 5.73×10-4) for its target antigen when compared to previously published results. A comparison with related populations of HCV-specific populations derived from the same individual and a second individual suggest that high-affinity TCR-pMHC interactions may be inherent to epitope identity and shape the phenotype of responses which has implications for rational TCR selection and design in the age of personalised immunotherapies.

Individuals with low socioeconomic status (SES) are at greater risk of contracting and developing severe disease compared to people with higher SES. Age, sex, host genetics, smoking, and Cytomegalovirus (CMV) serostatus are known to have a major impact on human immune responses and thus susceptibility to infection. However, the impact of SES on immune variability is not well understood or explored. Here, we used data from the Milieu Intérieur project, a study of 1,000 healthy volunteers with extensive demographic and biological data, to examine the effect of SES on immune variability. We developed an Elo-rating system using socioeconomic features such as education, income, and household to objectively rank SES in the 1,000 donors. We observed sex specific SES associations, such as females with a low SES having significantly higher frequency of CMV seropositivity compared to high SES females, and males from a low SES having significantly higher frequency of active smoking compared to high SES males. Using random forest models, we identified specific immune genes which were significantly associated with SES in both baseline and immune challenge conditions. Interestingly, many of the SES associations were sex-stimuli specific, highlighting the complexity of these interactions. Our study provides a new way of computing SES in human populations that can help identify novel SES associations and reinforces biological evidence for SES-dependent susceptibility to infection. This should serve as a basis for further understanding the molecular mechanisms behind socioeconomic status effects on immune responses and ultimately disease.

This journey traces the transition from a brief dentistry stint to a neuroimmunology exploration. The narrative unfolds through academic pursuits at the University of São Paulo, Brazil, and subsequent doctoral studies, reflecting on the initial idealism that shaped the pursuit of academia. An unexpected postdoctoral experience at the Centre de Physiopathologie de Toulouse Purpan in France introduced me to immunology, leading to an unexpected passion. Here, I explore uncertainties, decisions, and a pivotal move to Belgium, where collaboration with Adrian Liston at VIB-KU Leuven marked a maturity phase. Amid personal milestones like pregnancy and the challenges of balancing parenthood with a burgeoning career, I would like to highlight the crucial role of support systems and a thriving research environment. My journey so far culminates in the establishment of a lab, the pursuit of a permanent position, and the appointment as an assistant professor at KU Leuven.

Effective vaccines have reduced SARS-CoV-2 morbidity and mortality; however, the elderly remain the most at risk. Understanding how vaccines generate protective immunity, and how these mechanisms change with age is key for informing future vaccine design. Cytotoxic CD8+ T cells are important for killing virally infected cells, and vaccines that induce antigen specific CD8+ T cells in addition to humoral immunity provide an extra layer of immune protection. This is particularly important in cases where antibody titres are sub-optimal, as can occur in older individuals. Here, we show that in aged mice, spike-epitope specific CD8+ T cells are generated in comparable numbers to younger animals after ChAdOx1 nCoV-19 vaccination, although phenotypic differences exist. This demonstrates that ChAdOx1 nCoV-19 elicits a good CD8+ T cell response in older bodies, but that typical age-associated features are evident on these vaccine reactive T cells.