Public engagement is increasingly central to research, especially in biomedical fields, fostering dialogue between scientists and society, building trust and ensuring real-world relevance. However, as scientific and clinical progress accelerates, the gap between researchers and the public continues to widen, underscoring the need for deeper, more meaningful engagement. Despite the acknowledged value of public engagement for both researchers and the public, we know relatively little about academics' views on opportunities and potential barriers to participation. Using questionnaires and interviews, this study captured insights from 99 researchers and professionals across academic disciplines, career stages and geographical and cultural contexts. Respondents consistently regarded public engagement as an important and rewarding aspect of research, teaching and institutional responsibilities, with the potential to enhance public understanding, acceptance and societal impact. However, enthusiasm was tempered by persistent barriers, including academic workloads, inadequate resources and support, and a lack of formal recognition within career progression. Respondents emphasized the need for systemic reforms to enable greater participation, including tailored training, sustained funding and institutional frameworks that acknowledge and reward engagement. Overall, the findings demonstrate that while motivation for public engagement is widespread, structural and systemic challenges limit its full potential. Addressing these barriers requires coordinated action from universities, funders and policymakers to establish and embed public engagement more consistently as an integral component of academic research and higher education.

Invasive Staphylococcus aureus infections have high mortality and reinfection rates, in part due to impaired development of enduring antibody-mediated immunity. The generation of pathogen-specific antibodies is typically orchestrated and counter-regulated by CD4 + T follicular helper (T FH ) and T follicular regulatory (T FR ) cells respectively. Given their central roles in mediating adaptive immunity, these T cell subsets may form targets for S. aureus virulence factors, including superantigens (SAgs). SAgs force excessive production of proinflammatory cytokines which can trigger pathological cytokine ‘storms’, yet their impact on CD4 + T FH and T FR cells, and their contribution to impaired humoral immunity during S. aureus infections, remains poorly characterised. In this study, we characterised the phenotype and behaviour of CD4 + T FH and T FR cells in response to SAg stimulation, and the corresponding impact on antibody production. We found that SAgs elicited an in vitro expansion of circulating and tonsillar CD4 + T FR cells, which were polyfunctional with co-inhibitory signatures consistent with enhanced suppressive capacity. This expansion correlated with impaired plasmablast function and class-switched immunoglobulin production in human tonsil organoids which was rescued by interleukin-21 supplementation. Furthermore, acute expansions of CD4 + T FR cells were replicated during systemic S. aureus infection in vivo . Together, these findings establish CD4 + T FR cells as a target for SAg-mediated immune evasion and a novel target for vaccine development.

Public engagement is increasingly central to research, especially in biomedical fields, fostering dialogue between scientists and society, building trust and ensuring real-world relevance. However, as scientific and clinical progress accelerates, the gap between researchers and the public continues to widen, underscoring the need for deeper, more meaningful engagement. Despite the acknowledged value of public engagement for both researchers and the public, we know relatively little about academics' views on opportunities and potential barriers to participation. Using questionnaires and interviews, this study captured insights from 99 researchers and professionals across academic disciplines, career stages and geographical and cultural contexts. Respondents consistently regarded public engagement as an important and rewarding aspect of research, teaching and institutional responsibilities, with the potential to enhance public understanding, acceptance and societal impact. However, enthusiasm was tempered by persistent barriers, including academic workloads, inadequate resources and support, and a lack of formal recognition within career progression. Respondents emphasized the need for systemic reforms to enable greater participation, including tailored training, sustained funding and institutional frameworks that acknowledge and reward engagement. Overall, the findings demonstrate that while motivation for public engagement is widespread, structural and systemic challenges limit its full potential. Addressing these barriers requires coordinated action from universities, funders and policymakers to establish and embed public engagement more consistently as an integral component of academic research and higher education.

This Special Feature highlights the essential role of public engagement in building trust, raising awareness and improving understanding in infectious disease research, control and prevention. In fields such as immunology, microbiology and vaccinology, public engagement ensures that scientific advances are both communicated and applied effectively for improved global health. The present collection of articles presents creative and inspiring approaches to achieve this, from gamification tools that make complex concepts accessible to community-led initiatives that strengthen vaccine confidence among marginalized groups. Together, these contributions reinforce that public engagement requires dialogue, co-creation and the inclusion of diverse perspectives in research and policy. To maximize impact, engagement must be embedded as a core element of academic research and teaching, backed by training, recognition and sustained support. By advocating to make public engagement integral to infectious disease research and preparedness, this Special Feature demonstrates how collaboration between scientists and society can build more resilient and responsive health systems.

Funders increasingly emphasise patient and public involvement and engagement (PPIE) as an integral component of health and biomedical research. This shift reflects broader commitments to inclusivity, transparency and accountability, recognising that lived experiences enhance the relevance, feasibility and impact of research. PPIE can improve study design, recruitment and dissemination, supporting a transition from expert-led to co-created knowledge generation. However, funders sometimes provide little or no feedback on unsuccessful grant applications, typically citing capacity constraints. While some organisations offer constructive critique, others-especially smaller funders-do not, undermining the very participatory principles they aim to promote. Lack of feedback hampers researchers' professional development and disproportionately affects early-career academics, underrepresented groups and those without strong institutional support. It also risks discouraging public contributors who invest time and emotional effort in co-developing proposals, eroding trust and diminishing willingness to engage in the future. This disconnect between expectation and communication reinforces systemic inequities and risks reducing PPIE to a symbolic gesture. Strengthening response mechanisms is both a practical necessity and a moral and ethical obligation. Constructive critique is central to scientific progress; without it, the promise of PPIE to foster a reciprocal and transformative partnership risks being undermined, at a time when public trust in science is already fragile. We believe that current funding systems need to acknowledge their responsibility to deliver meaningful feedback, even within the realities of constrained resources.

Vaccination is arguably the most effective intervention in reducing the impact of infectious diseases. However, many vaccines provide only partial or transient protection, prompting the need for more effective solutions based on our growing understanding of the pivotal role of CD4+ T follicular helper (Tfh) cells in humoral immunity and how they interact with B cells. Here we review how γδ T cells can boost antibody responses via crosstalk with both Tfh and B cells, which could lead to new adjuvant strategies to improve vaccination efficacy, achieve long-lasting protective immunity and prevent major infectious diseases of global importance.

The immune system's primary functions include recognizing invading pathogens, controlling infections, and restoring tissue integrity. However, definitive evidence showing that an individual's local immune system can differentiate between bacterial pathogens to mount specific responses remains limited. In this study, we applied a machine learning approach to characterize immune responses in 82 peritoneal dialysis patients presenting with acute peritonitis. Immune profiles were obtained from peritoneal effluents on the day of infection onset, analyzing a comprehensive array of cellular and soluble markers, including local immune cell populations, inflammatory and regulatory cytokines, chemokines, and tissue damage-associated factors. Utilizing the Tsetlin Machine, a novel logic-based machine learning algorithm, we identified pathogen-specific immune fingerprints for different bacterial groups, each characterized by distinct biomarker profiles. Unlike traditional black-box models, the Tsetlin Machine expresses immune responses as transparent logical rules, enabling visual interpretation and supporting timely, informed antibiotic selection based on a patient's immune profile well before culture results become available. We also present during-and post-training techniques for feature and clause minimization to produce more concise rules, improve interpretability, and reduce computational cost. This capacity for transparent decision-making illustrates the potential of the Tsetlin Machine to analyze complex biomedical datasets and improve patient outcomes by delivering clear and actionable insights.

Vγ9/Vδ2 T cells represent the largest γδ T-cell population in human blood and possess a unique responsiveness towards microbial organisms by sensing the metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) in the context of the butyrophilin family members BTN2A1 and BTN3A1. Curiously, the bacterium Staphylococcus aureus does not produce HMB-PP but appears to be capable of inducing activation, cytokine expression and proliferation of Vγ9/Vδ2 T cells regardless, through a largely unknown mechanism. We here provide a comprehensive review of the existing literature around Vγ9/Vδ2 T-cell responses to S. aureus and discuss potential pathways, ligands and biological functions.

Gut symbionts condition mucosal immunity to resist infection by enteropathogens, but the specific microbes and mechanisms involved differ significantly between host species. In higher primates, bacterial metabolite HMB-PP is sensed by a specialized population of Vγ9Vδ2+T-cells, which we now report can potently suppress growth of endogenous fungi in human intestinal organ cultures. In healthy intestine, HMB-PP-stimulated Vδ2+T-cells restricted outgrowth of keystone fungus Candida albicans via a mechanism that required IL-22. In contrast, Crohn’s disease (CD) patients with reduced Vδ2+T-cell numbers displayed outgrowth of C. albicans strains that readily formed toxin-producing filaments, triggered neutrophil extracellular traps, and induced macrophage IL-1β release ex vivo . Genomic and proteomic analysis of the Candida isolates suggested increased tissue adhesion of CD-derived strains, which rapidly invaded the gut barrier in an ‘intestine-on-a-chip’ model. These data reveal that bacterial activation of Vδ2+T-cells suppresses fungal pathobionts in human gut via an IL-22-dependent mechanism that is dysregulated in CD. ### Competing Interest Statement KM has received consulting fees and sponsored research funding from Peel Therapeutics Inc. and is an inventor on patents related to NET-targeting in human disease (US11819540B2, US20180271953A1, US11426405B2). JOL has received consulting and/or speaker fees from AbbVie, AstraZeneca, Bristol Myers Squibb, Celgene, Celltrion, Engytix, Ferring Pharmaceuticals, Galapagos, Gilead, GSK, Janssen, Lilly, MSD, Napp, Pfizer, Shire, Takeda, and Vifor Pharma, as well as investigator-led research grants from AbbVie, Gilead, Pfizer, Shire, and Takeda. NEM has received consultancy fees and funding for research from ImCheck Therapeutics SAS and TC BioPharm. All other authors disclose no conflicts. Barts Charity, https://ror.org/0513pp416, MGU0465, G-002461 Wellcome Trust, https://ror.org/029chgv08, 223500/Z/21/Z, 214229/Z/18/Z Medical Research Council, https://ror.org/03x94j517, MR/R008302/1 Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, UKRI717

In this manuscript for the “Highlights of 2024” series, this is me trying to summarize recent discoveries regarding the emerging regulatory and effector roles of γδ T cells during sepsis, both in human patients and in mouse models. The new findings not only aid our understanding of key immunological and pathophysiological pathways that hit differently during the course of the disease but may also have clinical relevance for a life‐threatening condition that requires swift intervention and tailored patient management.

Motivation:The analysis of complex biomedical datasets is becoming central to understanding disease mechanisms, aiding risk stratification and guiding patient management. However, the utility of computational methods is often constrained by their lack of interpretability, which is particularly relevant in clinically critical areas where rapid initiation of targeted therapies is key. Results:To define diagnostically relevant immune signatures in peritoneal dialysis patients presenting with acute peritonitis, we analysed a comprehensive array of cellular and soluble parameters in cloudy peritoneal effluents. Utilizing Tsetlin Machines, a logic-based machine learning approach, we identified pathogen-specific immune fingerprints for different bacterial groups, each characterized by unique biomarker combinations. Unlike traditional 'black box' machine learning models, Tsetlin Machines identified clear, logical rules in the dataset that pointed towards distinctly nuanced immune responses to different types of bacterial infection. Importantly, these immune signatures could be easily visualized to facilitate their interpretation, thereby allowing for rapid, accurate and transparent decision-making. This unique diagnostic capacity of Tsetlin Machines could help deliver early patient risk stratification and support informed treatment choices in advance of conventional microbiological culture results, thus guiding antibiotic stewardship and contributing to improved patient outcomes. Availability and implementation:All underlying tools and the anonymized data underpinning this publication are available at https://github.com/anatoliy-gorbenko/biomarkers-visualization.

Natural killer (NK) cells are specialized lymphocytes that help protect against viruses and cancer. However, in the context of bacterial infections, NK cells can be harmful, rather than protective. Such immune pathogenesis by NK cells has been linked to the overproduction of proinflammatory cytokines like interferon-gamma (IFN-γ). In this context, IFN-γ–deficient mice display increased survival rates in response to Staphylococcus aureus (S. aureus) infection. However, little is known about how NK cells respond to S. aureus in humans, which causes life-threatening, invasive systemic infections with high mortality rates. In this study, we found that the peripheral blood of patients with bloodstream S. aureus infection was enriched for CD57− NKG2A+ NK cells with greater cytokine-producing capacity, compared to healthy controls and those hospitalized with Escherichia coli bloodstream infections. As a possible mechanistic cause, superantigens from S. aureus promoted the expansion of CD57− NKG2A+ NK cells that produced IFN-γ through a mechanism that appears to be IL-12 independent and exhibited reduced levels of CD16 compared to unstimulated NK cells. These data suggest that S. aureus bloodstream infection in humans promotes a phenotypic shift toward CD57− NKG2A+ NK cells with greater IFN-γ–producing capacity, providing a plausible way to promote inflammation-driven disease pathogenesis.

The need to empower people to understand their health and well-being has never been greater. However, current research culture does not necessarily prioritize public involvement and engagement, and many scientists are left under-equipped to reap its benefits. Here, we outline both the positive need for purposeful public involvement and engagement in biomedical research and major systemic challenges. While some of our examples stem from the UK, we believe the learnings from them have global significance.

Digital tools and online presence have become a cornerstone in public engagement and involvement strategy and delivery. We here describe the co-production process behind launching a new multilingual resource for schools in the United Kingdom and beyond, jointly between university scientists, engagement professionals, primary and secondary teachers, and web designers. The ‘Superbugs’ website aims at raising awareness and increasing the public understanding of the microbial world in, on, and around us—with a focus on infection, hygiene, and antimicrobial resistance—and attracted >19,000 online visitors, >33,500 page views, and > 775,000 Twitter impressions over the past 24 months. Superbugs.online is available in English, Welsh, Irish, and Scottish Gaelic, thus making it accessible to everyone in the United Kingdom and Ireland, regardless of the language in which they receive and deliver their science education. The website is easy to navigate and features background information, quizzes, animations, videos, illustrated stories, interactive timelines, games, and protocols for home experiments. All materials are presented in a non-prescriptive way, aimed at allowing flexibility for the materials to be adapted to the individual needs of teachers and pupils alike. Our study has led to a demonstrable impact on the co-production team and on pupils and teachers as key stakeholders, based on a comprehensive evaluation of the co-production process itself, the impact of the end product, and the creation of lasting relationships with stakeholders and co-producers, for the mutual benefit of everyone involved.

Sepsis affects 25 million children per year globally, leading to 2.9 million deaths and substantial disability in survivors. Extensive characterization of interactions between the host and bacteria in children is required to design novel preventive and therapeutic strategies tailored to this age group. Vγ9Vδ2 T cells are the first T cells generated in humans. These cells are defined by the expression of Vγ9Vδ2 T-cell receptors (TCRs, using the TRGV9 and TRDV2 gene segments), which react strongly against the prototypical bacterial phosphoantigen HMBPP. We investigated this reactivity by analyzing the TCR δ (TRD) repertoire in the blood of 76 children (0-16 years) with blood culture-proven bacterial sepsis caused by HMBPP-positive Escherichia coli or by HMBPP-negative Staphylococcus aureus or by HMBPP-negative Streptococcus pneumoniae. Strikingly, we found that S. aureus, and to a lesser extent E. coli but not S. pneumoniae, shaped the TRDV2 repertoire in young children (<2 years) but not in older children or adults. This dichotomy was due to the selective expansion of a fetal TRDV2 repertoire. Thus, young children possess fetal-derived Vγ9Vδ2 T cells that are highly responsive toward specific bacterial pathogens.

Since 2018, the ‘Superbugs’ initiative at Cardiff University (United Kingdom) has been delivering projects that take a research-driven approach to public engagement, involving rigorous evaluation of the methodologies of delivery and the mechanics of communication. The overall aim of Superbugs is to raise awareness and improve public knowledge of microbiology, infection and antimicrobial resistance (AMR). In the present project, four postgraduate students were recruited to undertake research projects as part of their Master of Science (MSc) studies. After a period of literature appraisals, the students chose to focus on the topic of personal and food hygiene and were tasked with collecting information on effective strategies for educating young children. Taking advantage of a focus group of primary school teachers, the students then designed evidence-informed educational activities and the evaluation strategies by which the impact of these would be assessed. A pilot delivery of these activities was carried out in a community setting at a local public library, before final delivery as part of a school outreach workshop. The MSc students produced three new elements of educational material; a story book, a treasure hunt and an interactive card game, primarily built around the concepts of challenge and gamification. Feedback collected from primary school pupils aged 6–7 years old and teachers indicated that the activities developed were successful in both being engaging to young people and resulting in an improved knowledge on the chosen topics. Taken together, we present evidence that postgraduate research training, underpinned by active and service learning, represents a valid and effective way of delivering impactful public engagement. In turn, the experience holds benefit for the students not only in terms of their academic study and core scientific skills, but also their wider appreciation and confidence in being effective engagers and science communicators.

Sepsis is characterized by a dysfunctional host response to infection culminating in life-threatening organ failure that requires complex patient management and rapid intervention. Timely diagnosis of the underlying cause of sepsis is crucial, and identifying those at risk of complications and death is imperative for triaging treatment and resource allocation. Here, we explored the potential of explainable machine learning models to predict mortality and causative pathogen in sepsis patients. By using a modelling pipeline employing multiple feature selection algorithms, we demonstrate the feasibility of identifying integrative patterns from clinical parameters, plasma biomarkers, and extensive phenotyping of blood immune cells. While no single variable had sufficient predictive power, models that combined five and more features showed a macro area under the curve (AUC) of 0.85 to predict 90-day mortality after sepsis diagnosis, and a macro AUC of 0.86 to discriminate between Gram-positive and Gram-negative bacterial infections. Parameters associated with the cellular immune response contributed the most to models predictive of 90-day mortality, most notably, the proportion of T cells among PBMCs, together with expression of CXCR3 by CD4+ T cells and CD25 by mucosal-associated invariant T (MAIT) cells. Frequencies of Vδ2+ γδ T cells had the most profound impact on the prediction of Gram-negative infections, alongside other T-cell-related variables and total neutrophil count. Overall, our findings highlight the added value of measuring the proportion and activation patterns of conventional and unconventional T cells in the blood of sepsis patients in combination with other immunological, biochemical, and clinical parameters.

Immunologists are very social people-they love to meet other immunologists and talk about immunology (and immunologists). Constantly! gamma delta T-cell researchers are no exception. On the contrary, as there are not so many of them compared to, say, researchers working on dendritic cells, they especially crave frequent interactions with like-minded scientists. This is where the technological solutions being developed during the coronavirus disease 2019 (COVID-19) pandemic come into play that have, almost overnight, allowed researchers to hold meetings and lectures online. We here describe how we set up the virtual 'gamma delta T Cell Club', a monthly webinar series that aims to bring the field closer together, and present our musings about what we have learned from this experience, which we hope is useful for other researchers interested in connecting online. We here describe how we set up the virtual 'gamma delta T Cell Club', a monthly webinar series that aims to bring the gamma delta field closer together, and present our musings about what we have learned from this experience, which we hope is useful for other researchers interested in connecting online. image

BACKGROUND:Involving and engaging the public in scientific research and higher education is slowly becoming the norm for academic institutions in the United Kingdom and elsewhere. Driven by a wide range of stakeholders including regulators, funders, research policymakers and charities public involvement and public engagement are increasingly seen as essential in delivering open and transparent activity that is relevant and positively impacts on our society. It is obvious that any activities involving and engaging members of the public should be conducted safely and ethically. However, it is not clear whether conducting activities ethically means they require ethical approval from a research ethics committee.MAIN BODY:Although there is some guidance available from government organisations (e.g. the UK Health Research Authority) to suggest ethical approval is not required for such activities, requests from funders and publishers to have ethical approval in place is commonplace in the authors' experience. We explore this using case studies from our own institution.CONCLUSION:We conclude that any public-facing activity with the purpose to systemically investigate knowledge, attitudes and experiences of members of the public as research and as human participants requires prior approval from an ethics committee. In contrast, engaging and involving members of the public and drawing on lived experience to inform aspects of research and teaching does not. However, lack of clarity around this distinction often results in the academic community seeking ethical approval 'just in case', leading to wasted time and resources and erecting unnecessary barriers for public involvement and public engagement. Instead, ethical issues and risks should be appropriately considered and mitigated by the relevant staff within their professional roles, be it academic or a professional service. Often this can involve following published guidelines and conducting an activity risk assessment, or similar. Moving forward, it is critical that academic funders and publishers acknowledge the distinction and agree on an accepted approach to avoid further exacerbating the problem.