Host Immune System Research Articles

Unraveling the Role of the Skin Microbiome in Immunodermatological Diseases: Implications for Therapeutic Interventions

The skin microbiome, comprising diverse microbial communities, plays a pivotal role in maintaining cutaneous homeostasis and modulating immune responses in immunodermatological diseases. This review provides an overview of recent research investigating the interplay between the skin microbiome and autoimmune, allergic, and inflammatory skin conditions, such as psoriasis, eczema, and acne vulgaris. This literature review was conducted using PubMed, searching the keywords "skin microbiome and immunodermatological diseases," "therapeutic interventions for skin microbiota," "skin disease and microbiome-host interaction," “immune response in dermatology,” “cutaneous microbiome,” "skin microbiome and allergies," "inflammatory skin conditions and microbiome," and “immune-mediated skin diseases.” A total of 53 articles were included in this review. Current evidence suggests that alterations in the skin microbiome composition, termed dysbiosis, may contribute to disease pathogenesis and exacerbate inflammation in immunodermatological disorders. Furthermore, microbial-derived metabolites and immune-modulating factors produced by commensal bacteria can influence local immune responses and skin barrier function. Future research directions include evaluating the mechanisms by which the skin microbiome interacts with the host immune system, identifying microbial biomarkers for disease diagnosis and prognosis, and exploring microbiome-targeted therapeutic interventions, such as probiotics, microbial transplantation, and microbial metabolite supplementation. By leveraging insights from microbiome research, personalized approaches to managing immunodermatological diseases may offer novel therapeutic avenues for restoring skin immune homeostasis and improving patient outcomes.

Hepatitis B

Hepatitis B is a viral infection caused by the Hepatitis B virus (HBV), primarily affecting the liver and leading to both acute and chronic disease. With over 250 million individuals suffering from chronic Hepatitis B, it poses a significant global health challenge, being a leading cause of liver cirrhosis, liver failure, and hepatocellular carcinoma. This study aims to elucidate the transmission pathways, treatment options, and necessary public health strategies for Hepatitis B. We analyze the modes of transmission, which include contact with infectious body fluids—primarily through perinatal transmission, unprotected sexual contact, and sharing contaminated needles. Despite the availability of an effective vaccine since the 1980s, Hepatitis B remains endemic in many parts of Asia and Africa due to limited immunization coverage. The pathogenesis of HBV involves complex interactions between the virus and the host immune system, potentially leading to liver inflammation and fibrosis. Clinical presentations vary widely, ranging from asymptomatic infections to severe liver disease. Current treatment options for chronic Hepatitis B include antiviral medications such as tenofovir and entecavir, which suppress viral replication but do not cure the infection. Recent advancements in therapeutic strategies, including novel antivirals and immune modulators, show promise for more effective management and potential cures in the future. Comprehensive public health strategies—such as vaccination, screening, and education—are crucial for controlling the spread of HBV and reducing the global burden of Hepatitis B-related complications.

Game-Changing Antibiotic Solutions for Chronic UTIs in Women

Urinary tract infections (UTIs) are prevalent in primary healthcare settings, with persistent recurrences posing significant challenges. These recurrences necessitate extended antibiotic use, adversely affecting patients' quality of life, mental health, and physical activity. The evolving defense mechanisms of bacteria against the host immune system and antibiotics complicate treatment. This article examines the pathomechanisms of recurrent UTIs, focusing on bacterial defense factors. Understanding these mechanisms is essential for developing innovative treatments, particularly non-antibiotic methods, to reduce antibiotic use and its associated side effects, thereby improving patients' overall well-being. The review synthesizes current knowledge on the pathomechanisms, diagnostics, and treatments for recurrent UTIs, emphasizing the impact on patients' mental and physical health. It highlights innovative, non-antibiotic treatment approaches.

A Study of Disease Prognosis in Lung Adenocarcinoma Using Single-Cell Decomposition and Immune Signature Analysis.

Background: The development of tumors is a highly complex process that entails numerous interactions and intricate relationships between the host immune system and cancer cells. It has been demonstrated in studies that the treatment response of patients can be correlated with the tumor microenvironment (TME). Consequently, the examination of diverse immune profiles within the TME can facilitate the elucidation of tumor development and the development of advantageous models for diagnoses and prognoses. Methods: In this study, we utilized a single-cell decomposition method to analyze the relationships between cell proportions and immune signatures in lung adenocarcinoma (LUAD) patients. Results: Our findings indicate that specific immune cell populations and immune signatures are significantly associated with patient prognosis. By identifying poor prognosis signatures (PPS), we reveal the critical role of immune profiles and cellular composition in disease outcomes, emphasizing their diagnostic potential for predicting patient prognosis. Conclusions: This study highlights the importance of immune signatures and cellular composition, which may serve as valuable biomarkers for disease prognosis in LUAD patients.

Aryl hydrocarbon receptor dynamics in esophageal squamous cell carcinoma: From immune modulation to therapeutic opportunities.

Esophageal squamous cell carcinoma (ESCC) is a substantial global health burden. Immune escape mechanisms are important in ESCC progression, enabling cancer cells to escape the surveillance of the host immune system. One key player in this process is the Aryl Hydrocarbon Receptor (AhR), which influences multiple cellular processes, including proliferation, differentiation, metabolism, and immune regulation. Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis, epithelial-mesenchymal transition, and immune escape. Targeting AhR signaling is a potential therapeutic approach for ESCC, with AhR ligands showing efficacy in preclinical studies. Additionally, modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention. This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.

Gene expression in soft-shell clam (Mya arenaria) transmissible cancer reveals survival mechanisms during host infection and seawater transfer.

Transmissible cancers are unique instances in which cancer cells escape their original host and spread through a population as a clonal lineage, documented in Tasmanian Devils, dogs, and ten bivalve species. For a cancer to repeatedly transmit to new hosts, these lineages must evade strong barriers to transmission, notably the metastasis-like physical transfer to a new host body and rejection by that host's immune system. We quantified gene expression in a transmissible cancer lineage that has spread through the soft-shell clam (Mya arenaria) population to investigate potential drivers of its success as a transmissible cancer lineage, observing extensive differential expression of genes and gene pathways. We observed upregulation of genes involved with genotoxic stress response, ribosome biogenesis and RNA processing, and downregulation of genes involved in tumor suppression, cell adhesion, and immune response. We also observe evidence that widespread genome instability affects the cancer transcriptome via gene fusions, copy number variation, and transposable element insertions. Finally, we incubated cancer cells in seawater, the presumed host-to-host transmission vector, and observed conserved responses to halt metabolism, avoid apoptosis and survive the low-nutrient environment. Interestingly, many of these responses are also present in healthy clam cells, suggesting that bivalve hemocytes may have inherent seawater survival responses that may partially explain why transmissible cancers are so common in bivalves. Overall, this study reveals multiple mechanisms this lineage may have evolved to successfully spread through the soft-shell clam population as a contagious cancer, utilizing pathways known to be conserved in human cancers as well as pathways unique to long-lived transmissible cancers.

Ume6-dependent pathways of morphogenesis and biofilm formation in Candida auris.

Candida auris is a yeast pathogen causing nosocomial outbreaks of candidemia. Its ability to adhere to inert surfaces and to be transmitted from one patient to another via medical devices is of particular concern. Like other Candida spp., C. auris has the ability to transition from the yeast form to pseudohyphae and to build biofilms. Moreover, some isolates have a unique capacity to form aggregates. These morphogenetic changes may impact virulence. In this study, we demonstrated the role of the transcription factor Ume6 in C. auris morphogenesis. Genetic hyperactivation of Ume6 induced filamentation and aggregation. The Ume6-hyperactivated strain (UME6HA) also exhibited increased adhesion to inert surface and formed biofilms of higher biomass compared to the parental strain. Transcriptomic analyses of UME6HA revealed enrichment of genes encoding for adhesins, proteins involved in cell wall organization, sterol biosynthesis, and aspartic protease activities. The three most upregulated genes compared to wild-type were those encoding for the agglutin-like sequence adhesin Als4498, the C. auris-specific adhesin Scf1, and the hypha-specific G1 cyclin-related protein Hgc1. The deletion of these genes in the UME6HA background showed that Ume6 controls filamentation via Hgc1 and aggregation via Als4498 and Scf1. Adhesion to inert surface was essentially triggered by Scf1. However, Als4498 and Hgc1 were also crucial for biofilm formation. Our data show that Ume6 is a universal regulator of C. auris morphogenesis via distinct modulators.IMPORTANCEC. auris represents a public health threat because of its ability to cause difficult-to-treat infections and hospital outbreaks. The morphogenetic plasticity of C. auris, including its ability to filament, to form aggregates or biofilms on inert surfaces, is important to the fungus for interhuman transmission, skin or catheter colonization, tissue invasion, antifungal resistance, and escape of the host immune system. This work deciphered the importance of Ume6 in the control of distinct pathways involved in filamentation, aggregation, adhesion, and biofilm formation of C. auris. A better understanding of the mechanisms of C. auris morphogenesis may help identify novel antifungal targets.

Cross-talk between macrophages and gut microbiota in inflammatory bowel disease: a dynamic interplay influencing pathogenesis and therapy.

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic immune-mediated gastrointestinal disorders. The etiology of IBD is multifactorial, involving genetic susceptibility, environmental factors, and a complex interplay between the gut microbiota and the host's immune system. Intestinal resident macrophages play an important role in the pathogenesis and progress of IBD, as well as in maintaining intestinal homeostasis and facilitating tissue repair. This review delves into the intricate relationship between intestinal macrophages and gut microbiota, highlighting their pivotal roles in IBD pathogenesis. We discuss the impact of macrophage dysregulation and the consequent polarization of different phenotypes on intestinal inflammation. Furthermore, we explore the compositional and functional alterations in gut microbiota associated with IBD, including the emerging significance of fungal and viral components. This review also examines the effects of current therapeutic strategies, such as 5-aminosalicylic acid (5-ASA), antibiotics, steroids, immunomodulators, and biologics, on gut microbiota and macrophage function. We underscore the potential of fecal microbiota transplantation (FMT) and probiotics as innovative approaches to modulate the gut microbiome in IBD. The aim is to provide insights into the development of novel therapies targeting the gut microbiota and macrophages to improve IBD management.

Fighting Pancreatic Cancer with a Vaccine-Based Winning Combination: Hope or Reality?

Pancreatic adenocarcinoma (PDA) represents the fourth leading cause of cancer-related mortality in the USA. Only 20% of patients present surgically resectable and potentially curable tumors at diagnosis, while 80% are destined for poor survival and palliative chemotherapy. Accordingly, the advancement of innovative and effective therapeutic strategies represents a pivotal medical imperative. It has been demonstrated that targeting the immune system represents an effective approach against several solid tumors. The immunotherapy approach encompasses a range of strategies, including the administration of antibodies targeting checkpoint molecules (immune checkpoint inhibitors, ICIs) to disrupt tumor suppression mechanisms and active immunization approaches that aim to stimulate the host's immune system. While vaccines have proved effective against infectious agents, vaccines for cancer remain an unfulfilled promise. Vaccine-based therapy targeting tumor antigens has the potential to be a highly effective strategy for initiating and maintaining T cell recognition, enhancing the immune response, and ultimately promoting cancer treatment success. In this review, we examined the most recent clinical trials that employed diverse vaccine types to stimulate PDA patients' immune systems, either independently or in combination with chemotherapy, radiotherapy, ICIs, and monoclonal antibodies with the aim of ameliorating PDA patients' quality of life and extend their survival.

Metabolic mediators: microbial-derived metabolites as key regulators of anti-tumor immunity, immunotherapy, and chemotherapy.

The human microbiome has recently emerged as a focal point in cancer research, specifically in anti-tumor immunity, immunotherapy, and chemotherapy. This review explores microbial-derived metabolites, emphasizing their crucial roles in shaping fundamental aspects of cancer treatment. Metabolites such as short-chain fatty acids (SCFAs), Trimethylamine N-Oxide (TMAO), and Tryptophan Metabolites take the spotlight, underscoring their diverse origins and functions and their profound impact on the host immune system. The focus is on SCFAs' remarkable ability to modulate immune responses, reduce inflammation, and enhance anti-tumor immunity within the intricate tumor microenvironment (TME). The review critically evaluates TMAO, intricately tied to dietary choices and gut microbiota composition, assessing its implications for cancer susceptibility, progression, and immunosuppression. Additionally, the involvement of tryptophan and other amino acid metabolites in shaping immune responses is discussed, highlighting their influence on immune checkpoints, immunosuppression, and immunotherapy effectiveness. The examination extends to their dynamic interaction with chemotherapy, emphasizing the potential of microbial-derived metabolites to alter treatment protocols and optimize outcomes for cancer patients. A comprehensive understanding of their role in cancer therapy is attained by exploring their impacts on drug metabolism, therapeutic responses, and resistance development. In conclusion, this review underscores the pivotal contributions of microbial-derived metabolites in regulating anti-tumor immunity, immunotherapy responses, and chemotherapy outcomes. By illuminating the intricate interactions between these metabolites and cancer therapy, the article enhances our understanding of cancer biology, paving the way for the development of more effective treatment options in the ongoing battle against cancer.

Regulation of immune responses to food by commensal microbes.

The increasing prevalence of immune-mediated non-communicable chronic diseases, such as food allergies, has prompted a deeper investigation into the role of the gut microbiome in modulating immune responses. Here, we explore the complex interactions between commensal microbes and the host immune system, highlighting the critical role of gut bacteria in maintaining immune homeostasis. We examine how modern lifestyle practices and environmental factors have disrupted co-evolved host-microbe interactions and discuss how changes in microbiome composition impact epithelial barrier function, responses to food allergens, and susceptibility to allergic diseases. Finally, we examine the potential of bioengineered microbiome-based therapies, and live biotherapeutic products, for reestablishing immune homeostasis to prevent or treat food allergies.

THE IMMUNOMODULATORY ROLE OF CYTOKINES IN THE PATHOGENESIS OF PERIODONTAL DISEASE

Background:Inflammatory periodontal diseases are one of the most acute problems of modern dentistry, which is associated with their widespread prevalence in the world. In the structure of periodontal diseases, periodontitis a leading place in the age group of 40-50 years. Many factors play a role in the etiology of periodontitis, the most important of which are the local microbiota and the host immune response. Cytokines play an extremely important role. Cytokines are key modulators of both homeostasis and inflammatory processes, acting in the first wave of responses against pathogens, stimuli at barrier sites and linking tissue cells to lymphocytes and additional cell populations. Objective:The aim of the study was to analyze modern literature on the role of cytokines in the etiology and pathogenesis of inflammatory periodontal diseases. Materials and methods:Data Extraction: A comprehensive electronic literature search was performed in the following databases:PubMed, Scopus,Web of Scienc, Google Scholar, EBSCO host from 2000 to 2024 terms: periodontitis, infection, inflammation, immunity, cytokines, interleukin. 124 articles were found and 50 full-text articles of high methodological quality were selected according to the review method used, the PRISMA. Inclusion criteria:included clinical trials, considered randomized controlled trials, cross-sectional studies, casecontrol studies, and cohort studies in human subjects that evaluated the current literature on the periodontitis, infection, inflammation, immunity, cytokines, interleukin written in English articles.There was no limitation on minimal quality, minimal sample size, or the number of patients. Exclusion criteria were:original primary studies, due to language limitations , abstracts, letters to the editor, book chapters, case reports, conference abstracts, duplicate publications, and in vitro and in vivo animal experimental studies. Result:Many factors of general and local origin are involved in the development and progression of inflammatory periodontal diseases. Microorganisms and their products cause activation of the host immune system, which results in the release of cytokines and other proinflammatory biomarkers that cause tissue damage. The inflammatory process in periodontal tissues progresses through various stages, beginning with the infiltration of immune cells into the gingival tissue. Immune cells secrete proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α),which further promote inflammation and tissue destruction. The interaction between bacterial biofilm and the immune response, which is mainly controlled by cytokines, determines the course of periodontal disease. Conclusion:The etiology and pathogenesis of periodontal disease is quite complex, diverse and not yet fully disclosed. Cytokines are control and modulate the immune response in periodontitis

Optimizing Pancreatic Cancer Therapy: The Promise of Immune Stimulatory Oncolytic Viruses.

Pancreatic cancer presents formidable challenges due to rapid progression and resistance to conventional treatments. Oncolytic viruses (OVs) selectively infect cancer cells and cause cancer cells to lyse, releasing molecules that can be identified by the host's immune system. Moreover, OV can carry immune-stimulatory payloads such as interleukin-12, which when delivered locally can enhance immune system-mediated tumor killing. OVs are very well tolerated by cancer patients due to their ability to selectively target tumors without affecting surrounding normal tissues. OVs have recently been combined with other therapies, including chemotherapy and immunotherapy, to improve clinical outcomes. Several OVs including adenovirus, herpes simplex viruses (HSVs), vaccinia virus, parvovirus, reovirus, and measles virus have been evaluated in preclinical and clinical settings for the treatment of pancreatic cancer. We evaluated the safety and tolerability of a replication-competent oncolytic adenoviral vector carrying two suicide genes (thymidine kinase, TK; and cytosine deaminase, CD) and human interleukin-12 (hIL12) in metastatic pancreatic cancer patients in a phase 1 trial. This vector was found to be safe and well-tolerated at the highest doses tested without causing any significant adverse events (SAEs). Moreover, long-term follow-up studies indicated an increase in the overall survival (OS) in subjects receiving the highest dose of the OV. Our encouraging long-term survival data provide hope for patients with advanced pancreatic cancer, a disease that has not seen a meaningful increase in OS in the last five decades. In this review article, we highlight several preclinical and clinical studies and discuss future directions for optimizing OV therapy in pancreatic cancer. We envision OV-based gene therapy to be a game changer in the near future with the advent of newer generation OVs that have higher specificity and selectivity combined with personalized treatment plans developed under AI guidance.

433 Use of polyclonal antibodies to improve the efficiency of rumen function

Abstract Technologies such as polyclonal antibody preparations (PAP) have been investigated as a tool to improve rumen function, by targeting specific bacteria or molecules. While PAP can be sourced from the serum of immunized mammals, isolating targeted avian-derived antibodies (immunoglobulin Y; IgY) from egg yolk gained popularity due to its reduced impact on hens and greater IgY concentration in yolks. Advantages of avian-derived PAP utilization include cost-effectiveness and convenient production, high stability, and reduced cross-reactivity compared with other PAPs. Furthermore, IgY does not activate the host immune complement system, as observed with PAP derived from mammalian serum. Several proposed strategies explain how PAP might protect the host. It is suggested that PAP can agglutinate bacteria, inhibit bacterial adhesion, suppress bacterial virulence factors, and neutralize toxins. Avian-derived PAP, mainly administered as a direct-fed product in beef and dairy cattle diets, has been studied for its impact on specific rumen microbial populations, especially during high-grain feeding. Research confirms the effectiveness of PAP-IgY in inhibiting the growth of targeted bacteria. In beef steers, feeding PAP-IgY against Streptococcus bovis and Fusobacterium necrophorum resulted in growth inhibition, while IgY against cellulolytic rumen bacteria also showed efficacy in reducing the growth of the targeted strains in vitro. In other studies, PAP-IgY targeting S. bovis and F. necrophorum increased ruminal pH in beef steers and heifers and dairy cows, while also cattle-fed PAP-IgY against F. necrophorum had reduced severity of liver abscesses. When performance was evaluated, PAP-IgY against S. bovis improved feed efficiency of feedlot beef steers, and milk production increased when dairy cows were supplemented with PAP-IgY against lipopolysaccharides, with no observed impact on cow health status. However, not all studies have consistently demonstrated positive effects of PAP-IgY on nutrient digestibility or on mitigating systemic inflammation during high-grain feeding. A recent study revealed that supplementation with PAP-IgY against Methanobrevibacter ruminantium M1 decreased methane output ex-situ and tended to increase molar proportion of propionate in beef steers. In summary, polyclonal antibody preparations, particularly avian-derived IgY, offer a promising alternative to improve rumen function and animal performance. This is evidenced by increased ruminal pH during high grain feeding, inhibition of targeted bacterial growth, and, most recently, methane reduction. However, not all studies demonstrate consistent effects regarding nutrient digestibility. Further research is needed to refine recommendations, including dosage and antibody combinations, and to explore the broader impacts of PAP-IgY supplementation on ruminal and systemic variables to optimize livestock performance.

The effect of Pseudomonas plecoglossicida vgrG gene on the immune response of hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂)

Pseudomonas plecoglossicida is a pathogen that causes visceral white spot disease that results in significant financial losses. Valine-glycine repeat protein G (VgrG) is one of the core components that make up the spike structure in the type VI secretion system (T6SS), which transports effectors and then contributes to bacterial virulence. However, the specific effect of VgrG on bacterial infection and host response process has not been clearly explained. Herein, we compared the pathogenicity of vgrG gene-deleted (ΔvgrG) strain, vgrG gene-complemented (C-ΔvgrG) strain, and the wild-type (NZBD9) strain of P. plecoglossicida to hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂). Compared to the wild strain, lost vgrG led to a higher survival rate, a lower bacterial load, and several mild pathological changes, such as fewer white nodules on the surface of the spleen and attenuated tissue damage. Moreover, the RNA-Seq of grouper spleen post-challenge indicated 3205 DEGs were involved in the two antibacterial responses, and the antigen presentation and processing pathway and the T-cell receptor signaling pathway were principal significant enrichment items. In summary, our data suggested that deletion of vgrG gene might reduce the pathogenicity of Pseudomonas plecoglossicida on hybrid grouper by making it less able to colonize the host and more easily cleared by the host immune system.

Protocol for a clinically annotated biorepository of samples from Australian immune-compromised patients to investigate the host–microbiome interaction

IntroductionThe human gut microbiota has the potential to modulate the outcomes of several human diseases. This effect is likely to be mediated through interaction with the host immune system. This...

Innate Immune Response and Epigenetic Regulation: A Closely Intertwined Tale in Inflammation.

Maintenance of delicate homeostasis is very important in various diseases because it ensures appropriate immune surveillance against pathogens and prevents excessive inflammation. In a disturbed homeostatic condition, hyperactivation of immune cells takes place and interplay between these cells triggers a plethora of signaling pathways, releasing various pro-inflammatory cytokines such as Tumor necrosis factor alpha (TNFα), Interferon-gamma (IFNƴ), Interleukin-6 (IL-6), and Interleukin-1 beta (IL-1β), which marks cytokine storm formation. To be precise, dysregulated balance can impede or increase susceptibility to various pathogens. Pathogens have the ability to hijack the host immune system by interfering with the host's chromatin architecture for their survival and replication in the host cell. Cytokines, particularly IL-6, Interleukin-17 (IL-17), and Interleukin-23 (IL-23), play a key role in orchestrating innate immune responses and shaping adaptive immunity. Understanding the interplay between immune response and the role of epigenetic modification to maintain immune homeostasis and the structural aspects of IL-6, IL-17, and IL-23 can be illuminating for a novel therapeutic regimen to treat various infectious diseases. In this review, the light is shed on how the orchestration of epigenetic regulation facilitates immune homeostasis.

Galloyl-boosted gold nanorods: Unleashing personalized cancer immunotherapy potential

Cancer immunotherapy has emerged as a potent treatment strategy by harnessing the host immune system to target cancer cells. However, challenges including low tumor vaccine immunogenicity and tumor heterogeneity hinder its clinical efficacy. To address these issues, we propose a novel nanoplatform integrating photothermal material gold nanorods (GNRs) with polyphenols for enhanced immunotherapy efficacy via photothermal therapy. Polyphenols, natural compounds with phenolic hydroxyl groups, are known for their ability to bind tightly to various molecules, making them ideal for antigen capture. We synthesized GNRs modified with polyphenols (GNR-PA and GNR-GA) and demonstrated their ability to induce immunogenic cell death upon laser irradiation, releasing tumor-associated antigens (TAAs). The surface polyphenols on GNRs effectively captured released TAAs to shield them from clearance. In vivo studies confirmed increased accumulation of GNR-GA in lymph nodes and enhanced dendritic cell maturation, leading to promoted effector T cell infiltration into tumors. Furthermore, treatment combined with PD-1/PD-L1 pathway blockade demonstrated potent tumor regression and systemic immunotherapy efficacy. Our findings highlight the potential of this photothermal nanoplatform as a promising strategy to overcome the limitations of current cancer immunotherapy approaches and improve therapeutic outcomes.

Effects of Schistosoma haematobium infection and treatment on the systemic and mucosal immune phenotype, gene expression and microbiome: A systematic review.

Urogenital schistosomiasis caused by Schistosoma haematobium affects approximately 110 million people globally, with the majority of cases in low- and middle-income countries. Schistosome infections have been shown to impact the host immune system, gene expression, and microbiome composition. Studies have demonstrated variations in pathology between schistosome subspecies. In the case of S. haematobium, infection has been associated with HIV acquisition and bladder cancer. However, the underlying pathophysiology has been understudied compared to other schistosome species. This systematic review comprehensively investigates and assimilates the effects of S. haematobium infection on systemic and local host mucosal immunity, cellular gene expression and microbiome. We conducted a systematic review assessing the reported effects of S. haematobium infections and anthelmintic treatment on the immune system, gene expression and microbiome in humans and animal models. This review followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42022372607). Randomized clinical trials, cohort, cross-sectional, case-control, experimental ex vivo, and animal studies were included. Two reviewers performed screening independently. We screened 3,177 studies and included 94. S. haematobium was reported to lead to: (i) a mixed immune response with a predominant type 2 immune phenotype, increased T and B regulatory cells, and select pro-inflammatory cytokines; (ii) distinct molecular alterations that would compromise epithelial integrity, such as increased metalloproteinase expression, and promote immunological changes and cellular transformation, specifically upregulation of genes p53 and Bcl-2; and (iii) microbiome dysbiosis in the urinary, intestinal, and genital tracts. S. haematobium induces distinct alterations in the host's immune system, molecular profile, and microbiome. This leads to a diverse range of inflammatory and anti-inflammatory responses and impaired integrity of the local mucosal epithelial barrier, elevating the risks of secondary infections. Further, S. haematobium promotes cellular transformation with oncogenic potential and disrupts the microbiome, further influencing the immune system and genetic makeup. Understanding the pathophysiology of these interactions can improve outcomes for the sequelae of this devastating parasitic infection.

Machine learning approaches identify immunologic signatures of total and intact HIV DNA during long-term antiretroviral therapy.

Understanding the interplay between the HIV reservoir and the host immune system may yield insights into HIV persistence during antiretroviral therapy (ART) and inform strategies for a cure. Here, we applied machine learning (ML) approaches to cross-sectional high-parameter HIV reservoir and immunology data in order to characterize host-reservoir associations and generate new hypotheses about HIV reservoir biology. High-dimensional immunophenotyping, quantification of HIV-specific T cell responses, and measurement of genetically intact and total HIV proviral DNA frequencies were performed on peripheral blood samples from 115 people with HIV (PWH) on long-term ART. Analysis demonstrated that both intact and total proviral DNA frequencies were positively correlated with T cell activation and exhaustion. Years of ART and select bifunctional HIV-specific CD4 T cell responses were negatively correlated with the percentage of intact proviruses. A leave-one-covariate-out inference approach identified specific HIV reservoir and clinical-demographic parameters, such as age and biological sex, that were particularly important in predicting immunophenotypes. Overall, immune parameters were more strongly associated with total HIV proviral frequencies than intact proviral frequencies. Uniquely, however, expression of the IL-7 receptor alpha chain (CD127) on CD4 T cells was more strongly correlated with the intact reservoir. Unsupervised dimension reduction analysis identified two main clusters of PWH with distinct immune and reservoir characteristics. Using reservoir correlates identified in these initial analyses, decision tree methods were employed to visualize relationships among multiple immune and clinical-demographic parameters and the HIV reservoir. Finally, using random splits of our data as training-test sets, ML algorithms predicted with approximately 70% accuracy whether a given participant had qualitatively high or low levels of total or intact HIV DNA . The techniques described here may be useful for assessing global patterns within the increasingly high-dimensional data used in HIV reservoir and other studies of complex biology.