Immune Lung Research Articles

Chronic Alcohol Intake Compromises Lung Immunity by Altering Immunometabolism in Humans and Mouse Models.

Chronic alcohol consumption disrupts lung immunity and host defense mechanisms, rendering individuals with alcohol use disorder more susceptible to developing inflammatory lung conditions with poor prognoses. Here, we focused on investigating the molecular and cellular effects of alcohol ingestion on lung immunity in male and female subjects using population-based human lung transcriptomics analysis and an experimental mouse model of chronic alcohol drinking using the National Institute on Alcohol Abuse and Alcoholism alcohol feeding model. Flow cytometry and transcriptomics analyses in lungs revealed a sexually dimorphic effect of chronic alcohol drinking on lung immunity in both human and mouse. Male lungs were more sensitive to chronic alcohol drinking-induced dysregulation of lung immunity compared with female lungs. Furthermore, comparative transcriptomics analysis using lungs and liver samples from matched human and mouse subjects demonstrated that lungs were more sensitive than liver to the effects of alcohol in downregulating immune-related genes and pathways. Furthermore, the transcriptomics analysis provided evidence that immunometabolic change is a central driver in lung alteration by downregulating the immune pathways and upregulating metabolic pathways. Chronic alcohol consumption resulted in reduced mTOR signaling and decreased immune cell populations. The mTOR signaling axis may serve as an upstream regulator of alcohol-induced dysregulation in lung immunity.

Single-cell spatiotemporal analysis reveals alveolar dendritic cell–T cell immunity hubs defending against pulmonary infection

How immune cells are spatiotemporally coordinated in the lung to effectively monitor, respond to, and resolve infection and inflammation in primed form needs to be fully illustrated. Here we apply immunocartography, a high-resolution technique that integrates spatial and single-cell RNA sequencing (scRNA-seq) through deconvolution and co-localization analyses, to the SARS-CoV-2-infected Syrian hamster model. We generate a comprehensive transcriptome map of the whole process of pulmonary infection from physiological condition, infection initiation, severe pneumonia to natural recovery at organ scale and single-cell resolution, with 142,965 cells and 45 lung lobes from 25 hamsters at 5 time points. Integrative analysis identifies that alveolar dendritic cell–T cell immunity hubs, where Ccr7+Ido1+ dendritic cells, Cd160+Cd8+ T cells, and Tnfrsf4+Cd4+ T cells physiologically co-localize, rapidly expand during SARS-CoV-2 infection, eliminate SARS-CoV-2 with the aid of Slamf9+ macrophages, and then restore to physiological levels after viral clearance. We verify the presence of these cell subpopulations in the immunity hubs in normal and SARS-CoV-2-infected hACE2 mouse models, as well as in publicly available human scRNA-seq datasets, demonstrating the potential broad relevance of our findings in lung immunity.

Dynamic responses of human lung innate and adaptive immune cells highlight the roles of genes at asthma risk loci.

The lung is a unique immunological niche with diverse immune cell types. The effects of stimulation through innate and adaptive immune receptors on human lung immune cells has largely been extrapolated from studies of blood immune cells. While multiple immune cell types and many genes have been implicated as contributing to asthma, the dynamics of these in human lung immune cells following activation will yield insights into asthma pathogenesis and lung immunity more broadly. Human lung immune cells from 6 donors were isolated. Mixed leukocytes were treated separately with lipopolysaccharide (LPS), F(ab)2-anti-human-IgM/IgG + IL4 and anti-CD3/CD28 for 4 and 18 hours and underwent single cell RNA sequencing (scRNAseq). Lung immune cell types were annotated, and gene expression compared across conditions. Genes at prior asthma-associated genetic loci were characterized across cell types, treatments and timepoints. Expression of non-classical class II genes associated with asthma, HLA-DQA2 and HLA-DQB2, and their protein products was characterized with immunohistochemistry. We characterized gene expression in 116,697 lung immune cells. Cell-, treatment-, and timepoint-specific effects on gene expression were detected in all lung immune cell populations. Correlation of gene expression between lung and blood lymphocyte populations decreased following stimulation. Among the genes that were differentially expressed, 97 receptor:ligand pairs had changes with treatments. 96.0% of genes at asthma risk loci demonstrated differential expression in at least one cell type and at least one treatment. B cells were the cell type with the highest expression of HLA-DQA2 and HLA-DQB2 which increased with anti-IgM/IgG treatment and the HLA-DQB2 protein was identified in lung B cells from a donor with asthma. Human lung immune activation elicits a broad range of cellular responses that deviate from those of blood immune cells and are relevant to asthma. Lung B cells expressing HLA-DQA2 and HLA-DQB2 appear to be involved in a novel antigen presentation pathway that contributes to asthma risk.

The gut microbiota and its metabolite butyrate shape metabolism and antiviral immunity along the gut-lung axis in the chicken

The gut microbiota exerts profound influence on poultry immunity and metabolism through mechanisms that yet need to be elucidated. Here we used conventional and germ-free chickens to explore the influence of the gut microbiota on transcriptomic and metabolic signatures along the gut-lung axis in poultry. Our results demonstrated a differential regulation of certain metabolites and genes associated with innate immunity and metabolism in peripheral tissues of germ-free birds. Furthermore, we evidenced the gut microbiota’s capacity to regulate mucosal immunity in the chicken lung during avian influenza virus infection. Finally, by fine-analysing the antiviral pathways triggered by the short-chain fatty acid (SCFA) butyrate in chicken respiratory epithelial cells, we found that it regulates interferon-stimulated genes (ISGs), notably OASL, via the transcription factor Sp1. These findings emphasize the pivotal role of the gut microbiota and its metabolites in shaping homeostasis and immunity in poultry, offering crucial insights into the mechanisms governing the communication between the gut and lungs in birds.

Rifaximin ameliorates influenza A virus infection-induced lung barrier damage by regulating gut microbiota

Prior research has indicated that the gut-lung-axis can be influenced by the intestinal microbiota, thereby impacting lung immunity. Rifaximin is a broad-spectrum antibacterial drug that can maintain the homeostasis of intestinal microflora. In this study, we established an influenza A virus (IAV)-infected mice model with or without rifaximin supplementation to investigate whether rifaximin could ameliorate lung injury induced by IAV and explore the molecular mechanism involved. Our results showed that IAV caused significant weight loss and disrupted the structure of the lung and intestine. The analysis results of 16S rRNA and metabolomics indicated a notable reduction in the levels of probiotics Lachnoclostridium, Ruminococcaceae_UCG-013, and tryptophan metabolites in the fecal samples of mice infected with IAV. In contrast, supplementation with 50 mg/kg rifaximin reversed these changes, including promoting the repair of the lung barrier and increasing the abundance of Muribaculum, Papillibacter and tryptophan-related metabolites content in the feces. Additionally, rifaximin treatment increased ILC3 cell numbers, IL-22 level, and the expression of RORγ and STAT-3 protein in the lung. Furthermore, our findings demonstrated that the administration of rifaximin can mitigate damage to the intestinal barrier while enhancing the expression of AHR, IDO-1, and tight junction proteins in the small intestine. Overall, our results provided that rifaximin alleviated the imbalance in gut microbiota homeostasis induced by IAV infection and promoted the production of tryptophan-related metabolites. Tryptophan functions as a signal to facilitate the activation and movement of ILC3 cells from the intestine to the lung through the AHR/STAT3/IL-22 pathway, thereby aiding in the restoration of the barrier.Key points• Rifaximin ameliorated IAV infection-caused lung barrier injury and induced ILC3 cell activation.• Rifaximin alleviated IAV-induced gut dysbiosis and recovered tryptophan metabolism.• Tryptophan mediates rifaximin-induced ILC3 cell activation via the AHR/STAT3/IL-22 pathway.

Optimized method for higher yield of alveolar macrophage isolation for ex vivo studies

Alveolar macrophages (AMs) are a fully differentiated lung-resident immune cell population and are a critical component of lung immunity. AMs can be easily isolated from mice via bronchoalveolar lavage fluid (BALF) collection. The quality and quantity of AMs in BALF isolation are critical for generating reliable and high-quality data for ex vivo studies. Traditional techniques use ice-cold (4°C) buffer to collect AMs in BALF and result in low yield. Hence, a new method that consistently gives a higher yield of AMs is needed. We demonstrate here an optimized method that significantly increases the quantity of AM recovery in BALF (>2.8 times than the traditional method). Our method uses a warm-buffer (37°C) containing EDTA. We compared the viability and functional parameters (cytokine/chemokine expression, phagocytosis) of AMs isolated by our new and traditional methods. Our study revealed that AMs collected using our method have similar viability and functional characteristics to those collected using traditional method. Hence, our new method can be used for the collection of a higher number of AMs without altering their function. This protocol might also be useful for isolating tissue-resident immune cells from other anatomical sites for ex vivo and other downstream applications.

Mitochondrial DNA-boosted dendritic cell-based nanovaccination triggers antitumor immunity in lung and pancreatic cancers

Low migratory dendritic cell (DC) levels pose a challenge in cancer immune surveillance, yet their impact on tumor immune status and immunotherapy responses remains unclear. We present clinical evidence linking reduced migratory DC levels to immune-cold tumor status, resulting in poor patient outcomes. To address this, we develop an autologous DC-based nanovaccination strategy using patient-derived organoid or cancer cell lysate-pulsed cationic nanoparticles (cNPs) to load immunogenic DC-derived microvesicles (cNPcancer cell@MVDC). This approach transforms immune-cold tumors, increases migratory DCs, activates Tcells and natural killer cells, reduces tumor growth, and enhances survival in orthotopic pancreatic and lung cancer models, surpassing conventional methods. Invivo imaging reveals superior cNPcancer cell@MVDC accumulation in tumors and lymph nodes, promoting immune cell infiltration. Mechanistically, cNPs enrich mitochondrial DNA, enhancing cGAS-STING-mediated DC activation and migration. Our strategy shifts cold tumors to a hot state, enhancing antitumor immunity for potential personalized cancer treatments.

CCL22 Induces the Polarization of Immature Dendritic Cells into Tolerogenic Dendritic Cells in Radiation-Induced Lung Injury through the CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1 Signaling Pathway.

Recruitment of immune cells to the injury site plays a pivotal role in the pathology of radiation-associated diseases. In this study, we investigated the impact of the chemokine CCL22 released from alveolar type II epithelial (AT2) cells after irradiation on the recruitment and functional changes of dendritic cells (DCs) in the development of radiation-induced lung injury (RILI). By examining changes in CCL22 protein levels in lung tissue of C57BL/6N mice with RILI, we discovered that ionizing radiation increased CCL22 expression in irradiated alveolar AT2 cells, as did MLE-12 cells after irradiation. A transwell migration assay revealed that CCL22 promoted the migration of CCR4-positive DCs to the injury site, which explained the migration of pulmonary CCR4-positive DCs in RILI mice invivo. Coculture experiments demonstrated that, consistent with the response of regulatory T cells in the lung tissue of RILI mice, exogenous CCL22-induced DCs promoted regulatory T cell proliferation. Mechanistically, we demonstrated that Dectin2 and Nr4a2 are key targets in the CCL22 signaling pathway, which was confirmed in pulmonary DCs of RILI mice. As a result, CCL22 upregulated the expression of PD-L1, IL-6, and IL-10 in DCs. Consequently, we identified a mechanism in which CCL22 induced DC tolerance through the CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1 pathway. Collectively, these findings demonstrated that ionizing radiation stimulates the expression of CCL22 in AT2 cells to recruit DCs to the injury site and further polarizes them into a tolerant subgroup of CCL22 DCs to regulate lung immunity, ultimately providing potential therapeutic targets for DC-mediated RILI.

Exercise may improve lung immunity after surgical stress: Evidence from a nephrectomy model via a bioinformatic analysis

Exercise may improve lung immunity after surgical stress: Evidence from a nephrectomy model via a bioinformatic analysis

Advanced nanomedicines and immunotherapeutics to treat respiratory diseases especially COVID-19 induced thrombosis

Immunotherapy and associated immune regulation strategies gained huge attraction in order to be utilized for treatment and prevention of respiratory diseases. Engineering specifically nanomedicines can be used to regulate host immunity in lungs in the case of respiratory diseases including coronavirus disease 2019 (COVID-19) infection. COVID-19 causes pulmonary embolisms, thus new therapeutic options are required to target thrombosis, as conventional treatment options are either not effective due to the complexity of the immune-thrombosis pathophysiology. In this review, we discuss regulation of immune response in respiratory diseases especially COVID-19. We further discuss thrombosis and provide an overview of some antithrombotic nanoparticles, which can be used to develop nanomedicine against thrombo-inflammation induced by COVID-19 and other respiratory infectious diseases. We also elaborate the importance of immunomodulatory nanomedicines that can block pro-inflammatory signalling pathways, and thus can be recommended to treat respiratory infectious diseases.

Case Commentary: Dual β-lactam as part of regimen to treat Mycobacterium abscessus lung disease.

Individuals with compromised lung function and immunity are susceptible to developing chronic Mycobacterium abscessus infection. Current treatment recommendations typically involve using one β-lactam antibiotic in combination with non-β-lactam antibiotics. However, a recent case study (B. Becken, K. M. Dousa, J. L. Johnson, S. M. Holland, and R. A. Bonomo, Antimicrob Agents Chemother 68:e00319-24, 2024, https://doi.org/10.1128/aac.00319-24) demonstrated successful treatment of chronic M. abscessus lung disease in a child using two β-lactam antibiotics simultaneously. This commentary reviews the emerging evidence and outstanding questions regarding dual β-lactam therapy for M. abscessus infections.

Integrated analysis of microbiome and host transcriptome unveils correlations between lung microbiota and host immunity in bronchoalveolar lavage fluid of pneumocystis pneumonia patients

ObjectiveThe lung microbiota of patients with pulmonary diseases is disrupted and impacts the immunity. The microbiological and immune landscape of the lungs in patients with pneumocystis pneumonia (PCP) remains poorly understood. MethodsMulti-omics analysis and machine learning were performed on bronchoalveolar lavage fluid to explore interaction between the lung microbiota and host immunity in PCP. Then we constructed a diagnostic model using differential genes with LASSO regression and validated by qPCR. The immune infiltration analysis was performed to explore the landscape of lung immunity in patients with PCP. ResultsPatients with PCP showed a low alpha diversity of lung microbiota, accompanied by the elevated abundance of Firmicutes, and the differential expressed genes (DEGs) analysis displayed a downregulation of MAPK signaling. The MAPK10, TGFB1, and EFNA3 indicated a potential to predict PCP (AUC = 0.86). The lung immune landscape in PCP showed the lower levels of naïve CD4+ T cells and activated dendritic cells. The correlation analysis of the MAPK signaling pathway-related DEGs and the differential microorganisms at the level of phylum showed that the Firmicutes was negatively correlated with these DEGs. ConclusionWe profiled the characteristics of lung microbiota and immune landscape in PCP, which may contribute to elucidating the mechanism of PCP.

Immunocompetent Alveolus-on-Chip Model for Studying Alveolar Mucosal Immune Responses.

We introduce an advanced immunocompetent lung-on-chip model designed to replicate the human alveolar structure and function. This innovative model employs a microfluidic-perfused biochip that supports an air-liquid interface mimicking the environment in the human alveoli. Tissue engineering is used to integrate key cellular components, including endothelial cells, macrophages, and epithelial cells, to create a representative tissue model of the alveolus. The model facilitates in-depth examinations of the mucosal immune responses to various pathogens, including viruses, bacteria, and fungi, thereby advancing our understanding of lung immunity. The primary goal of this protocol is to provide details for establishing this alveolus-on-chip model as a robust in vitro platform for infection studies, enabling researchers to closely observe and analyze the complex interactions between pathogens and the host's immune system within the pulmonary environment. This is achieved through the application of microfluidic-based techniques to simulate key physiological conditions of the human alveoli, including blood flow and biomechanical stimulation of endothelial cells, alongside maintaining an air-liquid interface crucial for the realistic exposure of epithelial cells to air. The model system is compatible with a range of standardized assays, such as immunofluorescence staining, cytokine profiling, and colony-forming unit (CFU)/plaque analysis, allowing for comprehensive insights into immune dynamics during infection. The Alveolus-on-chip is composed of essential cell types, including human distal lung epithelial cells (H441) and human umbilical vein endothelial cells (HUVECs) separated by porous polyethylene terephthalate (PET) membranes, with primary monocyte-derived macrophages strategically positioned between the epithelial and endothelial layers. The tissue model enhances the ability to dissect and analyze the nuanced factors involved in pulmonary immune responses in vitro. As a valuable tool, it should contribute to the advancement of lung research, providing a more accurate and dynamic in vitro model for studying the pathogenesis of respiratory infections and testing potential therapeutic interventions.

Comprehensive analysis of the gut microbiota in patients with chronic obstructive pulmonary disease of varying severity-A prospective, observational study

Accumulating evidence has highlighted the influence of the gut microbiota on lung immunity. We examined the effects of changes in intestinal microecology on the development of Chronic Obstructive Pulmonary Disease (COPD) and identified microbial biomarkers for acute exacerbations of COPD (AECOPD). Fecal samples were collected from 30 patients with stable COPD, 30 patients with AECOPD, and 10 healthy individuals. Fecal microbiological profiles were analyzed using 16S rRNA gene sequencing. The results showed a distinct difference in the bacterial community composition between the AECOPD, COPD, and healthy control groups. The COPD and AECOPD groups had higher levels of Firmicutes but lower levels of Bacteroidetes compared to the healthy control group at the phylum level. At the genus level, there was an increased abundance of Lachnoclostridium, Alistipes, Streptococcus, and Prevotella in COPD and AECOPD patients. Increasing levels of Lachnoclostridium and Prevotella may indicate an acute exacerbation of COPD. This study identified specific microbial biomarkers associated with AECOPD and characterized the composition of gut microbiota in patients with AECOPD.

Single-shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad, durable and protective systemic and mucosal immunity in mice

Current coronavirus disease 2019 vaccines face limitations including waning immunity, immune escape by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, limited cellular response, and poor mucosal immunity. We engineered a Clec9A-receptor binding domain (RBD) antibody construct that delivers the SARS-CoV-2 RBD to conventional type 1 dendritic cells. Compared with non-targeting approaches, single dose immunization in mice with Clec9A-RBD induced far higher RBD-specific antibody titers that were sustained for up to 21months after vaccination. Uniquely, increasing neutralizing and antibody-dependent cytotoxicity activities across the sarbecovirus family was observed, suggesting antibody affinity maturation over time. Consistently and remarkably, RBD-specific follicular T helper cells and germinal center B cells persisted up to 12months after immunization. Furthermore, Clec9A-RBD immunization induced a durable mono- and poly-functional T-helper 1-biased cellular response that was strongly cross-reactive against SARS-CoV-2 variants of concern, including Omicron subvariants, and with a robust CD8+ Tcell signature. Uniquely, Clec9A-RBD single-shot systemic immunization effectively primed RBD-specific cellular and humoral immunity in lung and resulted in significant protection against homologous SARS-CoV-2 challenge as evidenced by limited body weight loss and approximately 2 log10 decrease in lung viral loads compared with non-immunized controls. Therefore, Clec9A-RBD immunization has the potential to trigger robust and sustained, systemic and mucosal protective immunity against rapidly evolving SARS-CoV2 variants.

The dual role of 20(S)-protopanaxadiol in alleviating pulmonary fibrosis through the gut-lung axis

BackgroundPulmonary Fibrosis (PF) is a progressive lung disease characterized by the diffuse interstitial tissue, leading to severe breathing difficulties. The existing treatment methods are primarily aimed at slowing the progression of the disease, underscoring the urgent need to discover new drug interventions targeting novel sites. The "gut-lung axis" represents a complex bidirectional communication system where the gut microbiota not only influences lung immunity but also responds to lung-derived signals. Recent advances have uncovered that alterations in gut microbiota composition can significantly impact respiratory diseases, offering new insights into their pathogenesis and potential therapeutic approaches. MethodsThis study is based on the fundamental concepts of the lung-gut axis and our previous research, further exploring the potential mechanisms of 20(S)-Protopanaxadiol (PPD) in ginseng against PF. We utilized a bleomycin-induced mouse model of PF and employed metabolomics and 16S rRNA sequencing to investigate the pathways through which PPD regulates the pulmonary fibrosis process via the gut-lung axis. Finally, we employed strategies such as antibiotic-induced microbiota disruption and fecal microbiota transplantation (FMT) to provide a comprehensive perspective on how PPD regulates pulmonary fibrosis through gut microbiota. ResultsThe results of the bleomycin (BLM) mouse model of PF proved that PPD can directly act on the glycolysis- related metabolic reprogramming process in lung and the AMPK/STING pathway to improve PF. Combined the analysis of gut microbiota and related metabolites, we found that PPD can regulate the process of PF through the gut-lung axis target points G6PD and SPHK1. FMT and antibiotic-induced microbiota disruption further confirmed intermediate effect of gut microbiota in PF process and the treatment of PPD. Our study suggests that PPD can alleviate the process of pulmonary fibrosis either by directly acting on the lungs or by regulating the gut microbiota. ConclusionThis study positions PPD as a vanguard in the therapeutic landscape for pulmonary fibrosis, offering a dual mechanism of action that encompasses both modulation of gut microbiota and direct intervention at molecular targets. These insights highlight the immense therapeutic potential of harnessing the gut-lung axis.

Research Progress on Liposome Pulmonary Delivery of Mycobacterium tuberculosis Nucleic Acid Vaccine and Its Mechanism of Action.

Traditional vaccines have played an important role in the prevention and treatment of infectious diseases, but they still have problems such as low immunogenicity, poor stability, and difficulty in inducing lasting immune responses. In recent years, the nucleic acid vaccine has emerged as a relatively cheap and safe new vaccine. Compared with traditional vaccines, nucleic acid vaccine has some unique advantages, such as easy production and storage, scalability, and consistency between batches. However, the direct administration of naked nucleic acid vaccine is not ideal, and safer and more effective vaccine delivery systems are needed. With the rapid development of nanocarrier technology, the combination of gene therapy and nanodelivery systems has broadened the therapeutic application of molecular biology and the medical application of biological nanomaterials. Nanoparticles can be used as potential drug-delivery vehicles for the treatment of hereditary and infectious diseases. In addition, due to the advantages of lung immunity, such as rapid onset of action, good efficacy, and reduced adverse reactions, pulmonary delivery of nucleic acid vaccine has become a hot spot in the field of research. In recent years, lipid nanocarriers have become safe, efficient, and ideal materials for vaccine delivery due to their unique physical and chemical properties, which can effectively reduce the toxic side effects of drugs and achieve the effect of slow release and controlled release, and there have been a large number of studies using lipid nanocarriers to efficiently deliver target components into the body. Based on the delivery of tuberculosis (TB) nucleic acid vaccine by lipid carrier, this article systematically reviews the advantages and mechanism of liposomes as a nucleic acid vaccine delivery carrier, so as to lay a solid foundation for the faster and more effective development of new anti-TB vaccine delivery systems in the future.

Association between the lung microbiome and perioperative prognosis in lung transplant recipients.

Studies have confirmed that the lung microbiome of lung transplant recipients is altered and serves as a prognostic indicator for long-term mortality. Other studies reported that the lung microbiome affects host immunity and the transcriptome. However, the lung microbiome composition at the early post-transplant period following lung transplantation is unclear, and the relationship of the lung microbiome with pulmonary immunity and the host transcriptome is also not well understood. We hypothesize that changes in the lung microbiome composition in the early post-transplant period may have a predictive value for perioperative outcomes following lung transplantation and that the lung microbiome is correlated with pulmonary immunity and the host transcriptome. Thus, this prospective study aimed at observing the lung microbiome composition in the early post-transplant period and the impact of the lung microbiome on pulmonary cytokines and the host transcriptome. Our findings will help us gain a comprehensive understanding of the distribution and significance of the lung microbiome in the early post-transplant period. An observational study was conducted to identify the lung microbiome and the host transcriptome characteristics using next-generation sequencing. Luminex was employed for quantifying alveolar cytokines. Spearman's correlation analysis was utilized to assess the impact of the lung microbiome on pulmonary immunity and differentially expressed genes in patients who died perioperatively after lung transplantation. Patients with poor perioperative outcomes showed an increase in Mycoplasma and Arcobacter, a decrease of Gemella, and increased interleukin (IL)-10, IL-1β, and tumor necrosis factor (TNF)-α concentration. The lung microbiome correlates with lung immunity in lung transplant recipients. In the death group, the function of differentially expressed genes is associated with cell apoptosis, and promoting TNF production is upregulated. The lung microbiome is related to differentially expressed genes between the two groups. The lung microbiome and cytokines can be considered as potential biomarkers for early prognosis in lung transplant recipients. The lung microbiome is associated with both lung immunity and differentially expressed genes in lung transplant recipients.

Emerging concepts in alcohol, infection & immunity: A summary of the 2023 alcohol and immunology research interest group (AIRIG) meeting

On December 8th 2023, the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the University of Colorado Anschutz Medical Campus in Aurora, Colorado. The 2023 meeting focused broadly on how acute and chronic alcohol exposure leads to immune dysregulation, and how this contributes to damage in multiple tissues and organs. These include impaired lung immunity, intestinal dysfunction, autoimmunity, the gut-Central Nervous System (CNS) axis, and end-organ damage. In addition, diverse areas of alcohol research covered multiple pathways behind alcohol-induced cellular dysfunction, including inflammasome activation, changes in miRNA expression, mitochondrial metabolism, gene regulation, and transcriptomics. Finally, the work presented at this meeting highlighted novel biomarkers and therapeutic interventions for patients suffering from alcohol-induced organ damage.

Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis-A Potential Therapeutic Intervention to Improve Lung Health.

The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called "gut-lung axis". Perturbations in gut microbiota composition, termed dysbiosis, can have acute and chronic effects on the pathophysiology of lung diseases. Microbes and their metabolites in lung stimulate various innate immune pathways, which modulate the expression of the inflammatory genes in pulmonary leukocytes. For instance, gut microbiota-derived metabolites such as short-chain fatty acids can suppress lung inflammation through the activation of G protein-coupled receptors (free fatty acid receptors) and can also inhibit histone deacetylase, which in turn influences the severity of acute and chronic respiratory diseases. Thus, modulation of the gut microbiome composition through probiotic/prebiotic usage and fecal microbiota transplantation can lead to alterations in lung homeostasis and immunity. The resulting manipulation of immune cells function through microbiota and their key metabolites paves the way for the development of novel therapeutic strategies in improving the lung health of individuals affected with various lung diseases including SARS-CoV-2. This review will shed light upon the mechanistic aspect of immune system programming through gut and lung microbiota and exploration of the relationship between gut-lung microbiome and also highlight the therapeutic potential of gut microbiota-derived metabolites in the management of respiratory diseases.