Multiple sclerosis is a complex neurological disorder, involving both the adaptive and innate immune system as well as the CNS. The interaction between these systems is complex, and as such there is the potential for MS therapies to have conflicting effects in different tissues. It is therefore critical that in addition to tissue-specific studies, system-wide effects of potential therapeutic pathways are explored. The circulating protein Gas6 is a promising therapy to promote remyelination in people with multiple sclerosis. Gas6 is a ligand for the TAM family of receptor protein tyrosine kinases, that are widely expressed in the immune system and in the CNS, highlighting the potential for multi-system effects as a result of Gas6 treatment. In this study we demonstrate that global genetic deletion of either Gas6 or the Gas6 receptor Tyro3 results in reduced disease severity following induction of experimental immune encephalomyelitis in mice. The reduction in severity was accompanied by increased expression of IL-4 in Tyro3 KO mice, a cytokine known to be protective in inflammatory demyelination in mice. Conversely, loss of Tyro3 was associated with an increase in the expression of the pathological cytokine IL-17a. These data highlight the multi-faceted role of TAM receptor signalling in inflammatory demyelination.

Indigenous representation in Australian biomedical science and pharmacy research remains limited due to systemic barriers and culturally inappropriate frameworks. This case study highlights initiatives at the University of Newcastle (UoN) addressing these inequities. Central to this is the Indigenous Student Engagement Committee, which fosters Indigenous participation at all academic levels. Programs such as Yapug and Miroma Bunbilla, alongside culturally inclusive curricula and research fellowships, exemplify UoN’s commitment to supporting Indigenous researchers. Collaboration with local Aboriginal communities ensures these efforts are culturally safe and relevant. Early engagement with primary and secondary schools, facilitated by the Wollotuka Institute, creates pathways to demystify science and higher education. Programs such as laboratory work placements enhance accessibility and interest. At the tertiary level, indigenised curricula, mentorship, and dedicated cultural spaces support academic and personal success. Challenges remain, including inflexible funding models, the discomfort of non-Indigenous staff engaging in this space, and the need for inclusive recruitment practices. Addressing these requires sustained cultural capability training, mentorship programs, and funding structures accommodating community commitments. This case study showcases UoN’s culturally responsive strategies to increase Indigenous engagement in biomedical sciences. It underscores the necessity of systemic change, collaboration, and investment to create equitable pathways for Indigenous students and researchers. By prioritising cultural safety and inclusion, UoN offers a model for fostering diversity and building a more inclusive academic and research environment in Australia.

BACKGROUND: Responses to immune perturbations can vary greatly when comparing geographical regions such Europe versus South East Asia but also when comparing urban versus rural areas within a country. This can translate into differences in disease profiles or in responses to vaccines. However, even within an urban area, large differences in income settings can be seen. Therefore, it is also important to assess whether differences observed when comparing rural and urban residents can also be detected between high and low socioeconomic status (SES) within an urban center. AIM: To examine the immune profile of children of high versus low SES METHODS: Using mass cytometry, we profiled immune cells in finger-prick blood samples of children attending high and low SES schools in Makassar, Indonesia. RESULTS: Significant differences were found in the immune profiles of children from low versus high SES. Increased frequencies of entire and CD11c+ B cells, CD161+ T helper 2 cells and CTLA-4+ Tregs and HLA-DRdimCD163+ monocytes were seen in low SES children, whereas a trend towards expansion of T helper 1 cells was observed in the high SES group. CONCLUSION: Although differences in the immune system of populations living in rural versus urban areas have been documented, this study shows that within an urban center, the socioeconomic status can have a significant impact on the immune system of children. Such differences might contribute to variation seen in immune reactivity to allergens, autoantigens or vaccines, therefore SES should be factored in when studying responses to immune perturbations.

Regulation of cellular metabolism is a central element governing the fate and function of T cells. However, the in vivo metabolic characteristics of rare cells, such as non-lymphoid tissue T cells, are poorly understood due to experimental limitations. Most techniques measuring cell metabolism require large cell numbers. The recent SCENITHTM method allows studying the metabolism of rare cells by flow cytometry. However, this technique requires cells to be isolated and cultured ex vivo, which may alter their metabolism. Here, we propose a new experimental approach, called in vivo SCENITH, to investigate the cellular metabolism of T cells in vivo at steady state in the spleen and lungs. For this purpose, we administered the metabolic modulators directly in mice, instead of applying these reagents ex vivo, as in the classical SCENITHTM method. Whereas ex vivo manipulation impacted viability and phenotype of T cells, this toxic effect was not observed in the in vivo SCENITH. We observed that conventional and regulatory T cells shared similar metabolic profiles. Importantly, whereas spleen T cells used both oxidative phosphorylation and glycolysis, the metabolism of T cell in the lungs was mainly based on oxidative phosphorylation. Finally, metabolic inhibitors that interfere with protein translation and energy availability downregulated Foxp3 expression in regulatory T cells. These results describe an expansion of SCENITHTM that allows to measure the metabolic profile of rare cells in vivo, revealing a high dependence on oxidative phosphorylation of lung T cells.

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 a distinguished immunological process that assists the immune system in recognizing and responding effectively to eliminate foreign and self-pathogenic molecules. Improving the overall understanding of this immune mechanism during malaria infection is imperative. The full understanding of how this mechanism eradicates malaria parasites remains unclear, especially for Plasmodium falciparum. Which is an area requiring further broad investigations. In this context, previous studies have shown that various factors such as phagocyte cell subclasses, plasma protein molecules and Plasmodium evasion tactics influence the phagocytic process differently. However, the mechanisms underlying phagocytic activity during Plasmodium falciparum infection are still ambiguous. In this review, we aim to describe essential immunological aspects and the state of current knowledge on phagocytic activities in Plasmodium falciparum infection. We highlight the significant involvement of distinct active cells that induce phagocytosis. In addition, we discuss the implications and therapeutic approaches related to the effective phagocytic activity.  

Microbial life flourishes all around us and is invisible to the naked eye. Within this microscopic world are intracellular bacteria, including Salmonella enterica, Chlamydia trachomatis, and Orientia tsutsugamushi. By hijacking eukaryotic host cellular machinery and avoiding detection, these bacteria orchestrate their own survival and replication within host cells. The intricate nature of these interactions are usually communicated through images and graphical presentations, thereby excluding the low vision and blind communities. By taking part in the Sensory Science Exhibition, held at St Catharine’s College, University of Cambridge as part of the Cambridge Festival on the 18th March 2024, we sought to address this problem through creating a 3D mammalian cell and model bacteria. The aim of this tactile display was to guide participants through key aspects of intracellular bacterial life cycles such as host cell entry, S. enterica type three secretion system (T3SS) protein secretion, O. tsutsugamushi trafficking along microtubules, and C. trachomatis replication within an inclusion. We hope our multisensory conceptualisation of the intriguing lives of intracellular bacteria provided inclusive science communication to the low vision and blind communities.

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.