CCR5 and inflammatory storm.

Chemokines and their corresponding receptors play crucial roles in orchestrating inflammatory and immune responses, particularly in the context of pathological conditions disrupting the internal environment. Among these receptors, CCR5 has garnered considerable attention due to its significant involvement in the inflammatory cascade, serving as a pivotal mediator of neuroinflammation and other inflammatory pathways associated with various diseases. However, a notable gap persists in comprehending the intricate mechanisms governing the interplay between CCR5 and its ligands across diverse and intricate inflammatory pathologies. Further exploration is warranted, especially concerning the inflammatory cascade instigated by immune cell infiltration and the precise binding sites within signaling pathways. This study aims to illuminate the regulatory axes modulating signaling pathways in inflammatory cells by providing a comprehensive overview of the pathogenic processes associated with CCR5 and its ligands across various disorders. The primary focus lies on investigating the pathomechanisms associated with CCR5 in disorders related to neuroinflammation, alongside the potential impact of aging on these processes and therapeutic interventions. The discourse culminates in addressing current challenges and envisaging potential future applications, advocating for innovative research endeavors to advance our comprehension of this realm.

Higenamine exerts antidepressant effect by improving the astrocytic gap junctions and inflammatory response.

BACKGROUND: Depression is a refractory psychiatric disorder closely associated with dysfunction of the gap junctions (GJs) between astrocytes as well as neuroinflammation. Higenamine (Hig) is a potent cardiotonic ingredient in Fuzi (i.e., Aconitum carmichaeli Debx.) with anti-inflammatory and antioxidant effects, which has a significant protective effect on damaged nerve cells and has great potential for the treatment of neuropsychiatric diseases. METHODS: Rats were stimulated by chronic unpredictable stress (CUS) for 28 days while given Hig (5, 10, 20 mg/kg) and then analyzed behaviorally by the open field test, sucrose preference test, and forced swimming test. Changes in astrocyte GJs function and morphology were observed by dye transfer and transmission electron microscopy, respectively. Expression and phosphorylation of connexin 43 (Cx43) were analyzed by Western blot. Also, considering the close relationship between depression and neuroinflammation, we determined the inflammatory response in serum with ELISA kits and analyzed the expression of inflammation-related proteins with Western blot. RESULTS: Hig ameliorated CUS-induced depression-like behavior in rats. Hig administration improved gap junctional dysfunction in astrocytes, reduced gap junctional gaps and elevated the expression of Cx43 and decreased the phosphorylation of Cx43. Meanwhile, Hig administration was also able to attenuate the inflammatory response that occurs after CUS in rats. LIMITATIONS: For the role of Cx43 in depression, we did not validate it more deeply in animal models with knockout Cx43. In addition, GJs dysfunction might be associated with the inflammatory response seen in depression, but this needs to be further investigated. CONCLUSIONS: Hig ameliorates depression and exerts its antidepressant effect possibly by improving the dysfunctional GJs between astrocytes and the inflammatory response.

Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease.

Cardiovascular diseases (CVDs) continue to exert a significant impact on global mortality rates, encompassing conditions like pulmonary arterial hypertension (PAH), atherosclerosis (AS), and myocardial infarction (MI). Oxidative stress (OS) plays a crucial role in the pathogenesis and advancement of CVDs, highlighting its significance as a contributing factor. Maintaining an equilibrium between reactive oxygen species (ROS) and antioxidant systems not only aids in mitigating oxidative stress but also confers protective benefits on cardiac health. Herbal monomers can inhibit OS in CVDs by activating multiple signaling pathways, such as increasing the activity of endogenous antioxidant systems and decreasing the level of ROS expression. Given the actions of herbal monomers to significantly protect the normal function of the heart and reduce the damage caused by OS to the organism. Hence, it is imperative to recognize the significance of herbal monomers as prospective therapeutic interventions for mitigating oxidative damage in CVDs. This paper aims to comprehensively review the origins and mechanisms underlying OS, elucidate the intricate association between CVDs and OS, and explore the therapeutic potential of antioxidant treatment utilizing herbal monomers. Furthermore, particular emphasis will be placed on examining the cardioprotective effects of herbal monomers by evaluating their impact on cardiac signaling pathways subsequent to treatment.

A novel Z-type heterojunction Bi3O4Cl/Bi4O5I2 photocatalytic composite with broad-spectrum antibacterial activity and degradation properties.

At present, the sustainable development of humans is facing health problems and ecological imbalance caused by environmental pollution. To solve the bacteria, antibiotics and other pollutants in wastewater, Bi3O4Cl and Bi4O5I2 with appropriate bandgap width were selected to prepare Z-type heterojunction Bi3O4Cl/Bi4O5I2 photocatalytic materials by calcination method. Under LED light, the best sample Bi3O4Cl/Bi4O5I2-4 could completely inactivate Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in 30 min, Bacillus subtilis (B. subtilis) and Pseudomonas aeruginosa (P. aeruginosa) in 20 min, and degrade 70.6% of tetracycline (TC) and 97.4% of Rhodamine B (RhB). Photocurrent and electrochemical impedance tests (EIS) confirmed the high photocurrent response and low charge transfer resistance in the Bi3O4Cl/Bi4O5I2. The photocatalytic antibacterial and degradation mechanism of Z-type Bi3O4Cl/Bi4O5I2 heterojunction was verified by capture experiments. Thus, this study provides a compact and efficient photocatalyst with broad-spectrum antibacterial activity and degradation properties.

Targeting pyroptosis as a preventive and therapeutic approach for stroke.

Stroke has caused tremendous social stress worldwide, yet despite decades of research and development of new stroke drugs, most have failed and rt-PA (Recombinant tissue plasminogen activator) is still the accepted treatment for ischemic stroke. the complexity of the stroke mechanism has led to unsatisfactory efficacy of most drugs in clinical trials, indicating that there are still many gaps in our understanding of stroke. Pyroptosis is a programmed cell death (PCD) with inflammatory properties and are thought to be closely associated with stroke. Pyroptosis is regulated by the GSDMD of the gasdermin family, which when cleaved by Caspase-1/Caspase-11 into N-GSDMD with pore-forming activity can bind to the plasma membrane to form small 10-20 nm pores, which would allow the release of inflammatory factors IL-18 and IL-1ß before cell rupture, greatly exacerbating the inflammatory response. The pyroptosis occurs mainly in the border zone of cerebral infarction, and glial cells, neuronal cells and brain microvascular endothelial cells (BMECs) all undergo pyroptosis after stroke, which largely exacerbates the breakdown of the blood-brain barrier (BBB) and thus aggravates brain injury. Therefore, pyroptosis may be a good direction for the treatment of stroke. In this review, we focus on the latest mechanisms of action of pyroptosis and the process by which pyroptosis regulates stroke development. We also suggest potential therapeutic stroke drugs that target the pyroptosis pathway, providing additional therapeutic strategies for the clinical management of stroke. The role of pyroptosis after stroke. After stroke, microglia first rush to the damaged area and polarize into M1 and M2 types. Under the influence of various stimuli, microglia undergo pyroptosis, release pro-inflammatory factors, and are converted to the M1 type; astrocytes and neuronal cells also undergo pyroptosis under the stimulation of various pro-inflammatory factors, leading to astrocyte death due to increased osmotic pressure in the membrane, resulting in water absorption and swelling until rupture. BMECs, the main structural component of the BBB, also undergo pyroptosis when stimulated by pro-inflammatory factors released from microglia and astrocytes, leading to the destruction of the structural integrity of the BBB, ultimately causing more severe brain damage. In addition, GSDMD in neutrophils mainly mediate the release of NETs rather than pyroptosis, which also aggravates brain injury. IL-10=interleukin-10; TGF-ß = transforming growth factor-ß; IL-18=interleukin-18; IL-1ß = interleukin-1ß; TNF-α = tumor necrosis factor-α; iNOS=induced nitrogen monoxide synthase; MMPs=Matrix metalloproteinases; GSDMD = gasdermin D; BMECs=brain microvascular endothelial cells; BBB = blood-brain barrier.

A Review of Research on the Association between Neuron-Astrocyte Signaling Processes and Depressive Symptoms.

Depression is a mental illness that has a serious negative impact on physical and mental health. The pathophysiology of depression is still unknown, and therapeutic medications have drawbacks, such as poor effectiveness, strong dependence, adverse drug withdrawal symptoms, and harmful side effects. Therefore, the primary purpose of contemporary research is to understand the exact pathophysiology of depression. The connection between astrocytes, neurons, and their interactions with depression has recently become the focus of great research interest. This review summarizes the pathological changes of neurons and astrocytes, and their interactions in depression, including the alterations of mid-spiny neurons and pyramidal neurons, the alterations of astrocyte-related biomarkers, and the alterations of gliotransmitters between astrocytes and neurons. In addition to providing the subjects of this research and suggestions for the pathogenesis and treatment techniques of depression, the intention of this article is to more clearly identify links between neuronal-astrocyte signaling processes and depressive symptoms.

The mechanism of programmed death and endoplasmic reticulum stress in pulmonary hypertension.

Pulmonary hypertension (PH) was a cardiovascular disease with high morbidity and mortality. PH was a chronic disease with complicated pathogenesis and uncontrollable factors. PH was divided into five groups according to its pathogenesis and clinical manifestations. Although the treatment and diagnosis of PH has made great progress in the past ten years. However, the diagnosis and prognosis of the PAH had a great contrast, which was not conducive to the diagnosis and treatment of PH. If not treated properly, it will lead to right ventricular failure or even death. Therefore, it was necessary to explore the pathogenesis of PH. The problem we urgently need to solve was to find and develop drugs for the treatment of PH. We reviewed the PH articles in the past 10 years or so as well as systematically summarized the recent advance. We summarized the latest research on the key regulatory factors (pyroptosis, apoptosis, necroptosis, ferroptosis, and endoplasmic reticulum stress) involved in PH. To provide theoretical basis and basis for finding new therapeutic targets and research directions of PH.

Construction of a novel double S-scheme structure WO3/g-C3N4/BiOI: Enhanced photocatalytic performance for antibacterial activity.

In recent years, the threat to human health from bacteria in wastewater has attracted attention, and photocatalytic technology has emerged as a promising strategy for inactivating bacteria in water. Therefore, it is of great research value to develop a novel high-efficiency photocatalytic system with the visible light response. We successfully designed a double S-scheme heterojunction composite WO3/g-C3N4/BiOI (WCB) in this paper. The preparation of WCB composites was demonstrated by a series of characterizations, including X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and transmission electron microscopy (TEM). The antibacterial effects of photocatalysts against representative Gram-negative strain Escherichia coli (E. coli) and Gram-positive strain Staphylococcus aureus (S. aureus) were tested under LED light irradiation. The novel photocatalyst presented excellent antibacterial properties, inactivating E. coli in 12 min and S. aureus in 20 min. The bacterial cell inactivation process was studied by scanning electron microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM). Active species capture experiments show that the active species present in the WCB composites in the process of inactivating bacteria are h+, e-, OH and O2-. In conclusion, the synthesized double S-scheme WCB photocatalyst exhibits remarkable photocatalytic antibacterial activity under LED light and has broad prospects for practical application in water antibacterial treatment.

Fabrication of n-p ß-Bi2O3@BiOI core/shell photocatalytic heterostructure for the removal of bacteria and bisphenol A under LED light.

A novel n-p ß-Bi2O3@BiOI core/shell heterostructure was successfully constructed by a facile ultrasonication method. SEM, TEM, XRD and XPS confirmed the core/shell structure. UV-vis indicated the composite had good absorption of visible light. Photocurrent and electrochemical impedance analysis (EIS) revealed effective electron (e-) and hole (h+) separation efficiency in the core/shell hybrid structure, which induced a significantly improved photocatalytic activity. The ß-Bi2O3@BiOI photocatalyst effectively treated with Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and bisphenol A (BPA) under LED light, and presented better photocatalytic antibacterial performance than ß-Bi2O3 and BiOI. Trapping experiment revealed that h+ played an important role in photocatalytic reaction. The present work provided a novel LED light-activated photocatalyst that was efficient for antibacterial application.

CFP10-loaded PLGA nanoparticles as a booster vaccine confer protective immunity against Mycobacterium bovis.

Introduction: The limited efficacy of BCG (bacillus Calmette-Guérin) urgently requires new effective vaccination approaches for the control of tuberculosis. Poly lactic-co-glycolic acid (PLGA) is a prevalent drug delivery system. However, the effect of PLGA-based nanoparticles (NPs) against tuberculosis for the induction of mucosal immune response is no fully elucidated. In this study, we hypothesized that intranasal immunization with culture filtrate protein-10 (CFP10)-loaded PLGA NPs (CFP10-NPs) could boost the protective immunity of BCG against Mycobacterium bovis in mice. Methods: The recombinant protein CFP10 was encapsulated with PLGA NPs to prepare CFP10-NPs by the classical water-oil-water solvent-evaporation method. Then, the immunoregulatory effects of CFP10-NPs on macrophages in vitro and on BCG-immunized mice in vivo were investigated. Results: We used spherical CFP10-NPs with a negatively charged surface (zeta-potential -28.5 ± 1.7 mV) having a particle size of 281.7 ± 28.5 nm in diameter. Notably, CFP10-NPs significantly enhanced the secretion of tumor necrosis factor α (TNF-α) and interleukin (IL)-1ß in J774A.1 macrophages. Moreover, mucosal immunization with CFP10-NPs significantly increased TNF-α and IL-1ß production in serum, and immunoglobulin A (IgA) secretion in bronchoalveolar lavage fluid (BALF), and promoted the secretion of CFP10-specific interferon-γ (IFN-γ) in splenocytes of mice. Furthermore, CFP10-NPs immunization significantly reduced the inflammatory area and bacterial load in lung tissues at 3-week post-M. bovis challenge. Conclusion: CFP10-NPs markedly improve the immunogenicity and protective efficacy of BCG. Our findings explore the potential of the airway mucosal vaccine based on PLGA NPs as a vehicle for targeted lung delivery.

New Therapeutic Approaches to and Mechanisms of Ginsenoside Rg1 against Neurological Diseases.

Neurological diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), stroke, cerebral infarction, ischemia-reperfusion injury, depression and, stress, have high incidence and morbidity and often lead to disability. However, there is no particularly effective medication against them. Therefore, finding drugs with a suitable efficacy, low toxicity and manageable effects to improve the quality of life of patients is an urgent problem. Ginsenoside Rg1 (Rg1) is the main active component of ginseng and has a variety of pharmacological effects. In this review, we focused on the therapeutic potential of Rg1 for improving neurological diseases. We introduce the mechanisms of Ginsenoside Rg1 in neurological diseases, including apoptosis, neuroinflammation, the microRNA (miRNA) family, the mitogen-activated protein kinase (MAPK) family, oxidative stress, nuclear factor-κB (NF-κB), and learning and memory of Rg1 in neurological diseases. In addition, Rg1 can also improve neurological diseases through the interaction of different signal pathways. The purpose of this review is to explore more in-depth ideas for the clinical treatment of neurological diseases (including PD, AD, HD, stroke, cerebral infarction, ischemia-reperfusion injury, depression, and stress). Therefore, Rg1 is expected to become a new therapeutic method for the clinical treatment of neurological diseases.

Facile synthesizing Z-scheme Bi12O15Cl6/InVO4 heterojunction to effectively degrade pollutants and antibacterial under light-emitting diode light.

The design of a photocatalytic system with Z-scheme heterojunction is the key to charge separation. In this paper, a simple synthesis method was used to prepare Bi12O15Cl6/InVO4 photocatalyst. The synthesized photocatalyst can effectively degrade pollutants, and inactivate bacteria under LED light irradiation. The optimal ratio of 30% Bi12O15Cl6/InVO4 material effectively degraded 78.85% of TC and 97.83% of RhB within 90 min and inactivated Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in 40 min. This improvement in photocatalytic performance is mainly due to the formation of a Z-scheme heterojunction between Bi12O15Cl6 and InVO4, which produces effective charge separation and improves photocatalytic degradation and antibacterial activity. The capture experiment revealed the main active substances. The effects of catalyst dosage and pollutant concentration were investigated in details. The intermediates of TC degradation were identified by mass spectrometry (MS), and the possible photocatalytic degradation pathway was proposed. Capture experiment and related measurements proposed the Z-scheme mechanism. This work emphasizes the importance of heterogeneous structure construction and proposes feasible solutions for the rational design of catalysts with photodegradation and antibacterial properties under LED light.

Gut dysbacteriosis attenuates resistance to Mycobacterium bovis infection by decreasing cyclooxygenase 2 to inhibit endoplasmic reticulum stress.

The role of gut microbiota has been described as an important influencer of the immune system. Gut-lung axis is critical in the prevention of mycobacterium infection, but the specific mechanism, by which dysbiosis affects tuberculosis, has not been reported. In this study, we attempted to provide more information on how the gut-lung axis contributes to Mycobacterium bovis (M. bovis) infection. Mice are pre-treated with broad-spectrum antibiotics cocktail (Abx) to induce gut dysbiosis. Interestingly, dysbiosis of microbes showed a significant increase in the bacterial burden in the lungs and inhibited the level of COX-2. After faecal transplantation, cyclooxygenase 2 (COX-2) expression was restored and the inflammatory lesion in the lungs was reduced. Further research found that the deficiency of COX-2 inhibited endoplasmic reticulum stress (ER stress). This mechanism was completed by COX-2 interaction with BIP. Moreover, we found a positive feedback mechanism by which blocking ER stress could reduce COX-2 levels by the NF-κB pathway. Taken together, we reveal for the first time gut dysbacteriosis exacerbates M. bovis disease by limiting the COX-2/ER stress pathway. The finding strengthens the foundation of gut microbiota-targeted therapy for tuberculosis treatment.

Constructing an S-scheme CuBi2O4/Bi4O5I2 heterojunction for lightemittingdiode-driven pollutant degradation and bacterial inactivation.

The CuBi2O4/Bi4O5I2 S-scheme heterojunction structure was constructed by a hydrothermal and subsequent calcination route. The combination of CuBi2O4 and Bi4O5I2 produced excellent photocatalytic performance under an LED light. A series of technical characterizations, including X-ray diffraction (XRD), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), were used to determine the successful construction of S-scheme CuBi2O4/Bi4O5I2 composites. The improvement of photogenerated carrier separation efficiency helped to achieve the best photocatalytic performance of 37% CuBi2O4/Bi4O5I2, which can degrade tetracycline (TC) to 81.67% in 90 min, and completely inactivate Escherichia coli (E. coli) in 20 min and Staphylococcus aureus (S. aureus) in 40 min. The effects of some key parameters (such as the concentration of pollutants, the amount of catalyst, pH value of a solution, various inorganic anions and various water substrates) and the possible degradation path of tetracycline were systematically studied. Finally, the removal of pollutants and inactivation of bacterial mechanisms based on the S-scheme heterojunction (CuBi2O4/Bi4O5I2) was proposed. This study provides insight into the synthesis of S-scheme heterojunction photocatalysts, which can efficiently degrade organic pollutants and inactivate bacteria under LED light irradiation.

Prevention Effects of Chain Management on Pressure Ulcers of Hospitalized Patients.

The study focused on the preventive effects of the chain management model on pressure ulcers in the operating room. Sqoop big data collection module is used to collect patient information from various hospital information systems in a distributed manner. The data were from the clinical data center of the Zhongshan Hospital Xiamen University General Hospital, and 268 patients were selected as the research subjects. A chain management model is constructed, concerning the preventive measures, the management of each link, the perioperative pressure ulcer management, and the reporting of pressure ulcers. Then, the two groups were compared for the SAS and SDS scores before and after nursing, the pressure ulcer sites, pressure ulcer reporting rate, pressure ulcer staging, and nursing satisfaction. The results show that it is not that more collection modules will lead to better cluster performance and that the execution delay is caused by MapReduce requiring the JAVA virtual machine, and after reaching a certain point, the increase in the number of tasks will slow down the process, and as data size increases, DataNote has an expanded capability to analyze data. After nursing treatment, the SAS and SDS scores of the two groups of patients were significantly lower than before treatment (P < 0.05). The pressure ulcers were mainly distributed in the forehead, mandible, cheeks, front chest, and knees in the two groups, and the difference between the two groups was statistically significant (P < 0.05). The total satisfaction of the observation group was 93.28%, and the total satisfaction of the control group was 92.54%. The patients' satisfaction with the chain management model was higher than that of conventional nursing.

Social Force Model-Based Safety Evaluation of Intersections in Arterials Considering the Pedestrian Yield Rule.

To enhance the safety of pedestrians crossing the street, a series of new regulations regarding pedestrian yield has been proposed and widely implemented across cities. In this study, we first made some improvements to the social force model, in which pedestrian crossing at the intersection, drivers' psychology of giving way, vehicle yield to pedestrians, vehicle yield in different directions, the influence of pedestrians crossing boundaries, and signal lamp groups on pedestrian behavior were considered. Furthermore, pedestrian crossing and vehicle yield safety models were established, based on which the comprehensive safety evaluation model of intersections in arterials was established, in which two indices-(1) the safety degree of pedestrian crossings and (2) vehicle acceleration interference-were combined with the entropy weight method. Finally, four types of intersections in arterials were studied using a simulation: the intersections between different levels of arterials, and intersections with one-time and two-times pedestrian crossings. Moreover, safety evaluation and analysis of those intersections, considering the rule of pedestrian yield, were conducted combined with the trajectory data from the VISSIM simulation. The relevant results showed that for pedestrians crossing the street, the pedestrian safety of two-time crossing is significantly higher than that of one-time crossing, and compared with the arterial, the pedestrian crossing distance of the sub-arterial is shorter, and the pedestrian perception is safer. Moreover, due to the herd psychology effect, the increase in pedestrian flow volume improves the safety perception of pedestrians at the intersection.

Coordination of EZH2 and SOX2 specifies human neural fate decision.

Polycomb repressive complexes (PRCs) are essential in mouse gastrulation and specify neural ectoderm in human embryonic stem cells (hESCs), but the underlying molecular basis remains unclear. Here in this study, by employing an array of different approaches, such as gene knock-out, RNA-seq, ChIP-seq, et al., we uncover that EZH2, an important PRC factor, specifies the normal neural fate decision through repressing the competing meso/endoderm program. EZH2-/- hESCs show an aberrant re-activation of meso/endoderm genes during neural induction. At the molecular level, EZH2 represses meso/endoderm genes while SOX2 activates the neural genes to coordinately specify the normal neural fate. Moreover, EZH2 also supports the proliferation of human neural progenitor cells (NPCs) through repressing the aberrant expression of meso/endoderm program during culture. Together, our findings uncover the coordination of epigenetic regulators such as EZH2 and lineage factors like SOX2 in normal neural fate decision.

Koumiss promotes Mycobacterium bovis infection by disturbing intestinal flora and inhibiting endoplasmic reticulum stress.

Mycobacterium bovis is the causative agent of bovine tuberculosis and also responsible for serious threat to public health. Koumiss is a fermented mare's milk product, used as traditional drink. Here, we explored the effect of koumiss on gut microbiota and the host immune response against M bovis infection. Therefore, mice were treated with koumiss and fresh mare milk for 14 days before M bovis infection and continue for 5 weeks after infection. The results showed a clear change in the intestinal flora of mice treated with koumiss, and the lungs of mice treated with koumiss showed severe edema, inflammatory infiltration, and pulmonary nodules in M bovis-infected mice. Notably, we found that the content of short-chain fatty acids was significantly lower in the koumiss-treated group compared with the control group. However, the expression of endoplasmic reticulum stress and apoptosis-related proteins in the lungs of koumiss-treated mice were significantly decreased. Collectively, these findings suggest that koumiss treatment disturb the intestinal flora of, which is associated with disease severity and the possible mechanism that induces lungs pathology. Our current findings can be exploited further to establish the "gut-lung" axis which might be a novel strategy for the control of tuberculosis.

Caspase-1 inhibits IFN-ß production via cleavage of cGAS during M. bovis infection.

Mycobacterium bovis (M. bovis) infection triggers cytokine production via pattern recognition receptors. These cytokines include type I interferons (IFNs) and interleukin-1ß (IL-1ß). Excessive type I IFN levels impair host resistance to M. bovis infection. Therefore, strict control of type I IFN production is helpful to reduce pathological damage and bacterial burden. Here, we found that a deficiency in caspase-1, which is the critical component of the inflammasome responsible for IL-1ß production, resulted in increased IFN-ß production upon M. bovis infection. Subsequent experiments demonstrated that caspase-1 activation reduced cyclic GMP-AMP synthase (cGAS) expression, thereby inhibiting downstream TANK-binding kinase 1 (TBK1)- interferon regulatory factor 3 (IRF3) signaling and ultimately reducing IFN production. A deficiency in caspase-1 activation enhanced the bacterial burden during M. bovis infection in vitro and in vivo and aggravated pathological lesion formation. Thus, caspase-1 activation reduced IFN-ß production upon M. bovis infection by dampening cGAS-TBK1-IRF3 signaling, suggesting that the inflammasome protects hosts by negatively regulating harmful cytokines.