The stimulator of interferon genes (STING) is an adaptor protein involved in the activation of IFN-β and many other genes associated with the immune response activation in vertebrates. STING induction has gained attention from different angles such as the potential to trigger an early immune response against different signs of infection and cell damage, or to be used as an adjuvant in cancer immune treatments. Pharmacological control of aberrant STING activation can be used to mitigate the pathology of some autoimmune diseases. The STING structure has a well-defined ligand binding site that can harbor natural ligands such as specific purine cyclic di-nucleotides (CDN). In addition to a canonical stimulation by CDNs, other non-canonical stimuli have also been described, whose exact mechanism has not been well defined. Understanding the molecular insights underlying the activation of STING is important to realize the different angles that need to be considered when designing new STING-binding molecules as therapeutic drugs since STING acts as a versatile platform for immune modulators. This review analyzes the different determinants of STING regulation from the structural, molecular, and cell biology points of view.

Background: The morbidity and mortality associated with influenza viruses are a significant public health challenge. Annual vaccination against circulating influenza strains reduces hospitalisations and increases survival rates but requires a yearly redesign of vaccines against prevalent subtypes. The complex genetics of influenza viruses with high antigenic drift create an ongoing challenge in vaccine development to address dynamic influenza epidemiology. Understanding the evolution of influenza viruses and the vaccine's effectiveness against different types and subtypes is pivotal to designing public health measures against influenza.Methods: We conducted a systematic review and meta-analysis of 192 705 patients, collecting information on the incidence and severity of the disease. The results of this meta-analysis were further validated using data from 6 594 765 patients from TriNetX. We analysed the prevalence of the most common influenza A virus (IAV) subtypes (H1N1 and H3N2) and influenza B virus (IBV), as well as vaccination effectiveness against them in three age groups, given that age is associated with influenza disease severity.Results: Our analysis reflects that overall vaccination against H1N1 IAV and IBV is effective in reducing infection and influenza-related complications in children aged 65 years old. By contrast, while vaccination against H3N2 IAV is effective in protecting against infection in infants <5 years old, it provides reduced protection against infection in older individuals.Conclusions: Despite higher infection rates, vaccination against H3N2 remains as highly effective as vaccination against H1N1 and IBV in reducing influenza-related morbidity and mortality in all age groups. Detailing vaccine effectiveness in terms of infection protection and disease burden across different age groups is necessary for understanding vaccine impacts in terms of other outcomes,e.g.hospitalisations, mortality and disease severity; for improving vaccine formulations and public awareness; and for enhancing vaccination campaigns to improve coverage and public acceptance.

Background/Objectives: Celiac disease (CD) is an autoimmune disorder characterized by small intestinal enteropathy triggered by gluten ingestion, often associated with gut dysbiosis. The most effective treatment is strict adherence to a gluten-free diet (GFD), which alleviates symptoms. This study uniquely integrates taxonomic, functional, and resistance profiling to evaluate the gut microbiota of women with CD on a GFD. Methods: To evaluate the long-term impact of a GFD, this study analyzed the gut microbiota of 10 women with CD on a GFD for over a year compared to 10 healthy controls with unrestricted diets. Taxonomic diversity (16S rRNA gene sequencing and the analysis of α and β-diversity), metabolic functionality (Biolog EcoPlates^®), and antibiotic resistance profiles (Cenoantibiogram) were assessed. Results: Metagenomic analysis revealed no significant differences in taxonomic diversity but highlighted variations in the abundance of specific bacterial genera. Women with CD showed increased proportions of Bacteroides, Streptococcus, and Clostridium, associated with inflammation, but also elevated levels of beneficial genera such as Roseburia, Oxalobacter, and Paraprevotella. Despite no significant differences in metabolic diversity, higher minimum inhibitory concentrations (MICs) in women in the healthy control group suggest that dietary substrates in unrestricted diets may promote the proliferation of fast-growing bacteria capable of rapidly developing and disseminating antibiotic resistance mechanisms. Conclusions: These findings indicate that prolonged adherence to a GFD in CD supports remission of gut dysbiosis, enhances microbiota functionality, and may reduce the risk of antibiotic resistance, emphasizing the importance of dietary management in CD.

Dietary patterns, such as the Mediterranean diet (MD) and the Western diet (WD), influence gut microbiota composition and functionality, which play important roles in energy metabolism and nutrient absorption. Objectives: A descriptive cross-sectional study was designed to evaluate the gut microbiota of 19 Spanish adolescents and to investigate the association of MD and ultra-processed food (UPF) intake with microbial diversity and community structure. Methods: Functional diversity of gut microbiota was evaluated using Biolog EcoPlates, taxonomic composition was assessed with 16S rRNA sequencing via MinION, and phenotypic responses to antibiotics were analyzed using the cenoantibiogram technique under aerobic and anaerobic conditions. Results: Adolescents with higher adherence to the MD exhibited greater functional diversity, as per the Shannon–Weaver index. In addition, this group showed higher abundance of bacterial genera previously described as beneficial, such as Paraclostridium, Anaerobutyricum, Romboutsia, and Butyricicoccus. In contrast, adolescents reporting greater UPF intakes had a microbiota composition similar to those with low adherence to the MD, characterized by decreased abundance of beneficial genera. Regarding antibiotic resistance, significant differences were only observed under anaerobic conditions, with individuals with low adherence to the MD showing more sensitivity for most antibiotics tested. Conclusions: These results suggest that the MD promotes a healthier and more balanced gut environment, potentially improving metabolic functions in adolescents. Despite the lack of differences in α-diversity, comparisons of microbial community structure between adolescents following the MD and those with high UPF (characteristic of the WD) showed clear differences in terms of β-diversity. These findings suggest that dietary patterns influence the composition of the gut microbiota in a more complex manner, beyond just taxonomic richness. The outcomes of this exploratory study highlight opportunities for future research to deepen understanding of the long-term health implications of these dietary patterns, as well as the mechanisms regulating the composition, functionality, and phenotypic responses to antibiotics of gut microbial communities.

Secondary bacterial infections can significantly worsen the clinical course of influenza virus infections and are a leading cause of morbidity and mortality during seasonal influenza epidemics. Despite being a vaccine-preventable disease, influenza-related complications from secondary bacterial infections are an important cause of death, particularly among the elderly population. Streptococcus pneumoniae (Spn) is the most common agent responsible for influenza-related secondary bacterial infections. Influenza virus vaccination serves as an effective prophylactic strategy for preventing influenza and reducing the burden of influenza-associated pathology, including secondary bacterial infection. However, whether the protective effects of influenza virus vaccination differ in the context of a secondary Spn infection at the level of the host response remains poorly characterized. Here, we present a preclinical mouse model to examine the impact of influenza vaccination in scenarios involving single infections with influenza A virus H1N1 (NC99) or Spn serotype 1; simultaneous infection with both NC99 and Spn (coinfection), or NC99 infection followed by Spn infection seven days later (superinfection). A single dose of trivalent inactivated Influenza vaccine (TIV) is able to decrease infection lethality in both secondary bacterial infection scenarios. Protection is associated with reduction in both viral and bacterial titers, decreased production of pro-inflammatory cytokines, protection of alveolar macrophages, prevention of exacerbated lung neutrophil recruitment, modulation of neutrophil activation status, and induction of lung eosinophil recruitment and activation. These findings underscore the importance of influenza vaccination in modulating disease progression and preventing morbidity and mortality associated with secondary bacterial infections. IMPORTANCE: In this study, we show that a licensed influenza vaccine not only prevents severe disease upon influenza virus infection but also helps protect against enhanced morbidity due to co- or superinfection with S treptococcus pneumoniae in a mouse model. This protection correlates with better control of viral and bacterial titers, as well as with altered host immune responses during bacterial co- and superinfection, characterized by the recruitment of activated granulocytes.