Excessive Immune Response Research Articles

Loss-of-function/gain-of-function polymorphisms of the ATP sensitive P2X7R influence sepsis, septic shock, pneumonia, and survival outcomes.

Extracellular ATP (eATP) released from damaged cells activates the P2X7 receptor (P2X7R) ion channel on the surface of surrounding cells, resulting in calcium influx, potassium efflux and inflammasome activation. Inherited changes in the P2X7R gene (P2RX7) influence eATP induced responses. Single nucleotide polymorphisms (SNPs) of P2RX7 influence both function and signaling of the receptor, that in addition to ion flux includes pathogen control and immunity. Subjects (n = 105) were admitted to the ICU at the University Hospital Ulm, Germany between June 2018 and August 2019. Of these, subjects with a diagnosis of sepsis (n = 75), were also diagnosed with septic shock (n = 24), and/or pneumonia (n = 42). Subjects with pneumonia (n = 43) included those without sepsis (n = 1), sepsis without shock (n = 29) and pneumonia with septic shock (n = 13). Out of the 75 sepsis/septic shock patients, 33 patients were not diagnosed with pneumonia. Controls (n = 30) were recruited to the study from trauma patients and surgical patients without sepsis, septic shock, or pneumonia. SNP frequencies were determined for 16 P2RX7 SNPs known to affect P2X7R function, and association studies were performed between frequencies of these SNPs in sepsis, septic shock, and pneumonia compared to controls. The loss-of-function (LOF) SNP rs17525809 (T253C) was found more frequently in patients with septic shock, and non-septic trauma patients when compared to sepsis. The LOF SNP rs2230911 (C1096G) was found to be more frequent in patients with sepsis and septic shock than in non-septic trauma patients. The frequencies of these SNPs were even higher in sepsis and septic patients with pneumonia. The current study also confirmed a previous study by our group that showed a five SNP combination that included the GOF SNPs rs208294 (C489T) and rs2230912 (Q460R) that was designated #21211 was associated with increased odds of survival in severe sepsis. The results found an association between expression of LOF P2RX7 SNPs and presentation to the ICU with sepsis, and septic shock compared to control ICU patients. Furthermore, frequencies of LOF SNPs were found to be higher in sepsis patients with pneumonia compared to those without pneumonia. In addition, a five SNP GOF combination was associated with increased odds of survival in severe sepsis. These results suggest that P2RX7 is required to control infection in pneumonia and that inheritance of LOF variants increases the risk of sepsis when associated with pneumonia. This study confirms that P2RX7 genotyping in pneumonia may identify patients at risk of developing sepsis. The study also identifies P2X7R as a target in sepsis associated with an excessive immune response in subjects with GOF SNP combinations.

Pyroptosis: A major trigger of excessive immune response in the gingiva.

The gingival mucosal barrier, an important oral cavity barrier, plays a significant role in preventing pathogenic microorganism invasion and maintaining periodontal tissue health. Pathogenic microorganism invasion of the gingival mucosa produces a large number of cytokines. Among them, pyroptosis is an important player in exacerbating immune-inflammatory responses, leading to tissue destruction. However, the mechanism of pyroptosis and the immune response it triggers have not been fully elucidated. We provide an overview of recent advances in understanding gingival physical barrier pyroptosis and inflammation-induced hyperimmunity. PubMed, Web of Science databases were searched for articles, reviews, and clinical studies published until March 2024. We summarised the importance of the gingival barrier in terms of the functions of different cells, described the progress in research on gingival epithelial cell and gingival fibroblast pyroptosis and the immune-inflammatory response it induces, and discussed the relationship between pyroptosis and systemic diseases, association of multiple cell death systems. Finally, we propose future directions for pyroptosis research. Pyroptosis often triggers a range of inflammatory immune responses that lead to associated diseases. Therefore, further study of the molecular mechanisms of pyroptosis and the immune responses is warranted.

Poly (I:C)-Induced microRNA-30b-5p Negatively Regulates the JAK/STAT Signaling Pathway to Mediate the Antiviral Immune Response in Silver Carp (Hypophthalmichthys molitrix) via Targeting CRFB5.

In aquaculture, viral diseases pose a significant threat and can lead to substantial economic losses. The primary defense against viral invasion is the innate immune system, with interferons (IFNs) playing a crucial role in mediating the immune response. With advancements in molecular biology, the role of non-coding RNA (ncRNA), particularly microRNAs (miRNAs), in gene expression has gained increasing attention. While the function of miRNAs in regulating the host immune response has been extensively studied, research on their immunomodulatory effects in teleost fish, including silver carp (Hyphthalmichthys molitrix), is limited. Therefore, this research aimed to investigate the immunomodulatory role of microRNA-30b-5p (miR-30b-5p) in the antiviral immune response of silver carp (Hypophthalmichthys molitrix) by targeting cytokine receptor family B5 (CRFB5) via the JAK/STAT signaling pathway. In this study, silver carp were stimulated with polyinosinic-polycytidylic acid (poly (I:C)), resulting in the identification of an up-regulated miRNA (miR-30b-5p). Through a dual luciferase assay, it was demonstrated that CRFB5, a receptor shared by fish type I interferon, is a novel target of miR-30b-5p. Furthermore, it was found that miR-30b-5p can suppress post-transcriptional CRFB5 expression. Importantly, this study revealed for the first time that miR-30b-5p negatively regulates the JAK/STAT signaling pathway, thereby mediating the antiviral immune response in silver carp by targeting CRFB5 and maintaining immune system stability. These findings not only contribute to the understanding of how miRNAs act as negative feedback regulators in teleost fish antiviral immunity but also suggest their potential therapeutic measures to prevent an excessive immune response.

TOLL-LIKE RECEPTORS AND BRONCHIAL ASTHMA: PART 1

Bronchial asthma is a chronic disease of the respiratory tract, which is formed by the action of endogenous factors and environmental influences. At the same time, T-helpers of the second type play a major role in the development of bronchial asthma, causing hyperreactivity and inflammation of the respiratory tract. However, the data that bronchial asthma in most cases is an allergic, eosinophilic, T-helper-mediated disease of the second type is insufficient to establish complete control over the course of disease. This is probably due to the fact that endogenous factors play an important role in the pathogenesis of asthma, knowledge of which is currently limited. Toll-like receptors are an established element of the development of bronchial asthma. Their insufficient function or, conversely, the launch of an excessive immune response is associated with the initiation of the disease or its exacerbations. Expanding the understanding of Toll-like receptors leads not only to a more detailed understanding of the pathogenesis of bronchial asthma, but also to the application of this knowledge in practice.

Identification of hub genes and therapeutic siRNAs to develop novel adjunctive therapy for Duchenne muscular dystrophy

ObjectiveDuchenne muscular dystrophy (DMD) is a devastating X-linked neuromuscular disorder caused by various defects in the dystrophin gene and still no universal therapy. This study aims to identify the hub genes unrelated to excessive immune response but responsible for DMD progression and explore therapeutic siRNAs, thereby providing a novel treatment.MethodsTop ten hub genes for DMD were identified from GSE38417 dataset by using GEO2R and PPI networks based on Cytoscape analysis. The hub genes unrelated to excessive immune response were identified by GeneCards, and their expression was further verified in mdx and C57 mice at 2 and 4 months (M) by (RT-q) PCR and western blotting. Therapeutic siRNAs were deemed as those that could normalize the expression of the validated hub genes in transfected C2C12 cells.Results855 up-regulated and 324 down-regulated DEGs were screened from GSE38417 dataset. Five of the top 10 hub genes were considered as the candidate genes unrelated to excessive immune response, and three of these candidates were consistently and significantly up-regulated in mdx mice at 2 M and 4 M when compared with age-matched C57 mice, including Col1a2, Fbn1 and Fn1. Furthermore, the three validated up-regulated candidate genes can be significantly down-regulated by three rational designed siRNA (p < 0.0001), respectively.ConclusionCOL1A2, FBN1 and FN1 may be novel biomarkers for DMD, and the siRNAs designed in our study were help to develop adjunctive therapy for Duchenne muscular dystrophy.

Multifunctional nanogel loaded with cerium oxide nanozyme and CX3CL1 protein: Targeted immunomodulation and retinal protection in uveitis rat model

Effectively addressing retinal issues represents a pivotal aspect of blindness-related diseases. Novel approaches involving reducing inflammation and rebalancing the immune response are paramount in the treatment of these conditions. This study delves into the potential of a nanogel system comprising polyethylenimine-benzene boric acid-hyaluronic acid (PEI-PBA-HA). We have evaluated the collaborative impact of cerium oxide nanozyme and chemokine CX3CL1 protein for targeted immunomodulation and retinal protection in uveitis models. Our nanogel system specifically targets the posterior segment of the eyes. The synergistic effect in this area reduces oxidative stress and hampers the activation of microglia, thereby alleviating the pathological immune microenvironment. This multifaceted drug delivery system disrupts the cycle of oxidative stress, inflammation, and immune response, suppressing initial immune cells and limiting local retinal structural damage induced by excessive immune reactions. Our research sheds light on interactions within retinal target cells, providing a promising avenue for the development of efficient and innovative drug delivery platforms.

Immunomodulatory Precision: A Narrative Review Exploring the Critical Role of Immune Checkpoint Inhibitors in Cancer Treatment

An immune checkpoint is a signaling pathway that regulates the recognition of antigens by T-cell receptors (TCRs) during an immune response. These checkpoints play a pivotal role in suppressing excessive immune responses and maintaining immune homeostasis against viral or microbial infections. There are several FDA-approved immune checkpoint inhibitors (ICIs), including ipilimumab, pembrolizumab, and avelumab. These ICIs target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L1). Furthermore, ongoing efforts are focused on developing new ICIs with emerging potential. In comparison to conventional treatments, ICIs offer the advantages of reduced side effects and durable responses. There is growing interest in the potential of combining different ICIs with chemotherapy, radiation therapy, or targeted therapies. This article comprehensively reviews the classification, mechanism of action, application, and combination strategies of ICIs in various cancers and discusses their current limitations. Our objective is to contribute to the future development of more effective anticancer drugs targeting immune checkpoints.

Regulation of Treg cells by cytokine signaling and co-stimulatory molecules.

CD4+CD25+Foxp3+ regulatory T cells (Tregs), a vital component of the immune system, are responsible for maintaining immune homeostasis and preventing excessive immune responses. This review explores the signaling pathways of the cytokines that regulate Treg cells, including transforming growth factor beta (TGF-β), interleukin (IL)-2, IL-10, and IL-35, which foster the differentiation and enhance the immunosuppressive capabilities of Tregs. It also examines how, conversely, signals mediated by IL-6 and tumor necrosis factor -alpha (TNF-α) can undermine Treg suppressive functions or even drive their reprogramming into effector T cells. The B7 family comprises indispensable co-stimulators for T cell activation. Among its members, this review focuses on the capacity of CTLA-4 and PD-1 to regulate the differentiation, function, and survival of Tregs. As Tregs play an essential role in maintaining immune homeostasis, their dysfunction contributes to the pathogenesis of autoimmune diseases. This review delves into the potential of employing Treg-based immunotherapy for the treatment of autoimmune diseases, transplant rejection, and cancer. By shedding light on these topics, this article aims to enhance our understanding of the regulation of Tregs by cytokines and their therapeutic potential for various pathological conditions.

Helminth alleviates COVID-19-related cytokine storm in an IL-9-dependent way.

Hyperactivation of pro-inflammatory type 1 cytokines (e.g., tumor necrosis factor alpha [TNF-α] and interferon gamma [IFN-γ]) mirrors the inflammation of coronavirus disease 2019. Helminths could alleviate excessive immune responses. Here, helminth Trichinella spiralis (Ts) infection was shown to protect against TNF-α- and IFN-γ-induced shock. Mechanistically, Ts-induced protection was interleukin-9 (IL-9) dependent but not IL-4Rα. Recombinant IL-9 treatment not only improved the survival of wild-type mice with TNF-α- and IFN-γ-induced shock but also that of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected K18-human angiotensin-converting enzyme 2 (hACE2) mice, emphasizing the significance of IL-9 in alleviating cytokine storm syndromes during SARS-CoV-2 infection. Interestingly, Ts excretory/secretory (TsES)-induced protection was also observed in SARS-CoV-2 infection, indicating that identifying anti-inflammatory molecules from TsES could be a novel way to mitigate adverse pathological inflammation during pathogen infection.IMPORTANCESevere coronavirus disease 2019 (COVID-19) is linked to cytokine storm triggered by type 1 pro-inflammatory immune responses. TNF-α and IFN-γ shock mirrors cytokine storm syndromes, including COVID-19. Helminths (e.g., Trichinella spiralis, Ts) can potently activate anti-inflammatory type 2 immune response. Here, we found that helminth Ts-induced protection against TNF-α and IFN-γ shock was IL-9 dependent. Treatment with recombinant IL-9 could protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in K18-hACE2 mice. Helminth Ts excretory/secretory (TsES) products also ameliorated SARS-CoV-2 infection-related cytokine storm. In conclusion, our study emphasizes the significance of IL-9 in protecting from cytokine storm syndromes associated with SARS-CoV-2 infection. Anti-inflammatory molecules from TsES could be a new source to mitigate adverse pathological inflammation associated with infections, including COVID-19.

Manifestation and associated factors of systemic and local allergy among patients with allergic fungal rhinosinusitis: An observational study.

Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis, characterized by excessive immune responses to environmental molds or fungi. The diagnosis and classification of AFRS into systemic and local types remain clinically challenging due to overlapping characteristics. This study investigated the prevalence of AFRS, its manifestation and associated factors in systemic and local AFRS. A total of 200 patients diagnosed with fungal rhinosinusitis underwent both skin provocation tests (SPT) and nasal provocation tests (NPT) to confirm AFRS and classify systemic and local types. Patients were considered to have AFRS if either the SPT or NPT was positive. Among these, patients with systemic AFRS were those who had a SPT positive. Local AFRS was when patients had a negative SPT and a positive NPT. Medical history, serum total IgE level, nasal endoscopy examinations, and CT scans were also recorded. Most patients were female (65.8%), with a mean age of 55.6 years (SD = 14.4). Based on the SPT and NPT results, 31% of patients (n = 62) were diagnosed with AFRS. Among these, 54.8% (n = 34) had systemic AFRS, while 45.2% (n = 28) had local AFRS. Patients with AFRS exhibited significantly higher levels of total IgE, eosinophils, and more pronounced signs and symptoms compared to those without AFRS. However, no statistically significant differences were observed between patients with systemic AFRS and those with local AFRS. AFRS was prevalent in our study. Among patients with AFRS, both systemic AFRS and local AFRS were also prevalent. While allergic indicators and clinical presentations can aid in AFRS diagnosis, minimal distinctions were observed between systemic and local AFRS. A comprehensive assessment incorporating both local and systemic allergic responses through provocation tests, such as a combination of skin and nasal tests, is imperative for optimizing AFRS diagnosis and management.

CLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.

Gastrointestinal Tract and Kidney Injury Pathogenesis in Post-COVID-19 Syndrome.

COVID-19 is a global health emergency that requires worldwide collaboration to control its spread. The scientific community is working to understand the different aspects of the post-COVID-19 syndrome and potential treatment strategies. Interestingly, there have been reports of gastrointestinal tract (GIT) involvement in the post-COVID-19 syndrome, suggesting the presence of both severe and mild GIT disorders. The development of the post-COVID-19- GIT syndrome involves various factors, such as impaired GIT mucosa cells, disruptions in the feeling of satiety, reduced blood supply due to the formation of small blood clots, and increased prostaglandin secretion caused by an excessive immune response. GIT symptoms have been observed in around 16% of COVID-19 patients. Other complications include kidney damage and prolonged impairment in the filtration and excretion functions of the glomeruli and tubules. The pathogenesis of post-COVID-19 renal syndrome involves factors, like an overactive immune response, reduced lung perfusion and oxygenation, viral infection in kidney tissues, endothelial dysfunction, and decreased blood volume. Roughly 20% of hospitalized patients experience renal manifestations after recovering from COVID-19.

The Role of Macrophage Death in Periodontitis: A Review.

Periodontitis, an infectious inflammatory disease influenced by various factors, disrupts the delicate balance between the host microbiota and immunity. The resulting excessive immune response exacerbates the progressive destruction of the supporting periodontal tissue. Macrophages are essential elements of the host innate immune system. They are pivotal components in the periodontal immune microenvironment and actively participate in both physiological and pathological processes of periodontal tissue. When confronted with periodontitis-related irritant factors, macrophages may differentiate to pro- or anti-inflammatory subtypes that affect tissue homeostasis. Additionally, macrophages may die in response to bacterial infections, potentially affecting the severity of periodontitis. This article reviews the typical mechanisms underlying macrophage death and its effects on periodontitis. We describe five forms of macrophage death in periodontitis: apoptosis, pyroptosis, necroptosis, ferroptosis, and ETosis. Our review of macrophage death in the pathophysiology of periodontitis enhances comprehension of the pathogenesis of periodontitis that will be useful for clinical practice. Although our review elucidates the complex mechanisms by which macrophage death and inflammatory pathways perpetuate periodontitis, unresolved issues remain, necessitating further research.

The possible link between aluminum phosphide poisoning and NLRP3 inflammasome

Aluminum phosphide (AlP) is a fumigant used to control pests. However, human exposure to this substance can lead to poisoning. AlP reacts with gastric acid and water to release phosphine (PH3). This toxic gas affects the mitochondria and quickly enters the bloodstream. This gas impairs the mitochondria's ability to generate ATP, leading to oxidative stress, mitochondrial dysfunction, and damage to mitochondrial DNA (mt-DNA). Mitochondria release damage-associated molecular patterns (DAMPs) to shield cells from stress and stimulate the innate immune system.Nonetheless, if mitochondrial homeostasis is disrupted, an excessive immune response can occur, causing organ dysfunction. Mitochondrial reactive oxygen species (mt-ROS) and mt-DNA act as DAMPs. Upon recognition of DAMPs, the inflammasome is activated, causing inflammation. The nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) gene on chromosome 1's extended arm encodes a protein that triggers the human inflammasome. NLRP3 is the most extensively researched inflammasome subfamily. It is essential to recognize that the pathophysiology of mitochondrial dysfunction and NLRP3 activation is complex and multifactorial, and a comprehensive approach may be needed to address both the underlying causes and downstream inflammatory responses effectively. The cGAS-STING pathway is essential for immune responses, and targeting specific nodes can be beneficial. Therapeutic approaches include small molecule drugs, biologics, vaccines, and combination therapies. Since there is a significant relationship between mitochondrial events and NLRP3 activation, targeting this inflammasome could be a promising strategy for developing antidotes for AlP poisoning.

Dihydroartemisinin is an inhibitor of trained immunity through Akt/mTOR/HIF1α signaling pathway

Trained immunity is mechanistically defined as the metabolically and epigenetically mediated long-term functional adaptation of the innate immune system, characterized by a heightened response to a secondary stimulation. Given appropriate activation, trained immunity represents an attractive anti-infective therapeutic target. Nevertheless, excessive immune response and subsequent inflammatory cascades may contribute to pathological tissue damage, indicating that the negative impacts of trained immunity appear to be significant. In this study, we show that innate immune responses such as the production of extracellular traps, pro-inflammatory cytokines, and autophagy-related proteins were markedly augmented in trained BMDMs. Furthermore, heat-killed C. albicans priming promotes the activation of the AIM2 inflammasome, and AIM2−/− mice exhibit impaired memory response induced by heat-killed C. albicans. Therefore, we establish that the AIM2 inflammasome is involved in trained immunity and emerges as a promising therapeutic target for potentially deleterious effects. Dihydroartemisinin can inhibit the memory response induced by heat-killed C. albicans through modulation of mTOR signaling and the AIM2 inflammasome. The findings suggest that dihydroartemisinin can reduce the induction of trained immunity by heat-killed C. albicans in C57BL/6 mice. Dihydroartemisinin is one such therapeutic intervention that has the potential to treat of diseases characterized by excessive trained immunity.

USP18 Antagonizes Pyroptosis by Facilitating Selective Autophagic Degradation of Gasdermin D.

As a key executioner of pyroptosis, Gasdermin D (GSDMD) plays a crucial role in host defense and emerges as an essential therapeutic target in the treatment of inflammatory diseases. So far, the understanding of the mechanisms that regulate the protein level of GSDMD to prevent detrimental effects and maintain homeostasis is currently limited. Here, we unveil that ubiquitin-specific peptidase 18 (USP18) works as a negative regulator of pyroptosis by targeting GSDMD for degradation and preventing excessive innate immune responses. Mechanically, USP18 recruits E3 ubiquitin ligase mind bomb homolog 2 (MIB2) to catalyze ubiquitination on GSDMD at lysine (K) 168, which acts as a recognition signal for the selective autophagic degradation of GSDMD. We further confirm the alleviating effect of USP18 on LPS-triggered inflammation invivo. Collectively, our study demonstrates the role of USP18 in regulating GSDMD-mediated pyroptosis and reveals a previously unknown mechanism by which GSDMD protein level is rigorously controlled by selective autophagy.

Bovine Colostrum miR-30a-5p Targets the NF-κB Signaling Pathway to Alleviate Inflammation in Intestinal Epithelial Cells.

Inflammatory bowel disease (IBD) is a common disease of the digestive system, and an excessive immune response mediated by the nuclear factor κ-B (NF-κB) signaling pathway is an essential etiology. Recent studies have found that bovine milk exosomes can improve intestinal mucosal health by delivering microRNA (miRNA), but the mechanism of action is so far unknown. In the present study, we analyzed the differential expression profiles of miRNA in colostrum and mature milk exosomes using high-throughput sequencing, based on the demonstration that colostrum exosomes inhibit the lipopolysaccharide (LPS)-induced intestinal epithelial NF-κB inflammatory pathway better than mature milk exosomes. The bta-miR-30a-5p, which is specifically highly expressed in colostrum, was screened, and its predicted target gene TRAM was found to be closely related to the NF-κB signaling pathway by functional enrichment analysis. Further, we used gene overexpression and silencing techniques and found that the bta-miR-30a-5p transfection treatment was confirmed to inhibit LPS-induced NF-κB signaling pathway activation and downstream pro-inflammatory factor expression, while the expression of its potential target gene, TRAM, was also suppressed. It is hypothesized that the high expression of bta-miR-30a-5p in colostrum, which targets TRAM to inhibit the downstream NF-κB inflammatory pathway, may be one of the molecular mechanisms responsible for its superior effect on resisting inflammatory attack compared to mature milk.

Immunopathology of emerging and re-emerging viral infections: an updated overview

Humankind has witnessed increased frequency of emerging and re-emerging viral diseases in the past few decades. The major categories of pathogenic emerging and re-emerging viral infections include respiratory, arthropod-borne and bat-borne zoonotic viruses. These viral infections are notorious for causing immune dysregulation and have the potential to mount excessive immune reaction, causing immunopathology that includes tissue injury, systemic inflammation, multi-organ failure and even death. A better understanding of the emerging or re-emerging viral-mediated immunomodulation is necessary for controlling the virus, while preventing severity of the disease associated with exaggerated immune response. In this article, we review the current understanding of emerging and re-emerging respiratory, arboviral and bat-borne zoonotic viruses; and consequent immune dysregulation or immunopathology associated with these viral infections.

Chronic inhalation of H2S in low concentration induces immunotoxicity and inflammatory effects in lung tissue of rats

Hydrogen sulfide (H2S) is a typical odour compound mainly causing respiratory and central nervous system symptoms. However, the immunotoxicity of inhaled H2S and the underlying mechanisms remain largely unknown. In this study, a low-dose inhalation exposure to H2S was arranged to observe inflammatory response and immunotoxicity in lung tissue of rats. Low concentrations of H2S exposure affected the immune level of pulmonary tissue and peripheral blood. Significant pathological changes in lung tissue in the exposure group were observed. At low concentration, H2S not only induced the upregulation of AQP-4 and MMP-9 expression but also stimulated immune responses, initiating various anti-inflammatory and inflammatory factors, altering tissue homeostatic environments. The TNF and chemokine signaling pathway played an important role which can promote the deterioration of pulmonary inflammatory processes and lead to lung injury and fibrosis. Excessive immune response causes an inflammatory effect and blood-gas barrier damage. These data will be of value in evaluating future occupational health risks and providing technical support for the further development of reliable, sensitive, and easy-to-use screening indicators of exposure injury.

Insights into the defensive roles of lncRNAs during Mycoplasma pneumoniae infection.

Mycoplasma pneumoniae causes respiratory tract infections, affecting both children and adults, with varying degrees of severity ranging from mild to life-threatening. In recent years, a new class of regulatory RNAs called long non-coding RNAs (lncRNAs) has been discovered to play crucial roles in regulating gene expression in the host. Research on lncRNAs has greatly expanded our understanding of cellular functions involving RNAs, and it has significantly increased the range of functions of lncRNAs. In lung cancer, transcripts associated with lncRNAs have been identified as regulators of airway and lung inflammation in a process involving protein complexes. An excessive immune response and antibacterial immunity are closely linked to the pathogenesis of M. pneumoniae. The relationship between lncRNAs and M. pneumoniae infection largely involves lncRNAs that participate in antibacterial immunity. This comprehensive review aimed to examine the dysregulation of lncRNAs during M. pneumoniae infection, highlighting the latest advancements in our understanding of the biological functions and molecular mechanisms of lncRNAs in the context of M. pneumoniae infection and indicating avenues for investigating lncRNAs-related therapeutic targets.