International Reviews of Immunology最新文献

Macrophages are the primary targets of mycobacterial infection, which plays crucial roles both in nonspecific defence (innate immunity) as well as specific defence mechanisms (adaptive immunity) by secreting various cytokines, antimicrobial mediators and presenting antigens to T-cells. Sequencing of the mycobacterial genome revealed that 10% of its coding ability is devoted to the Pro-Glu motif-containing (PE) and Pro-Pro-Glu motif-containing (PPE) family proteins. While the function of most of the genes belonging to the PE-PPE family initially remained unannotated, recent studies have shown that many proteins of this family play critical roles in bacterial growth and cell functions, and manipulation of host immune responses, indicating their potential roles in mycobacterial virulence. In this review, we have focussed on describing the immunological importance of particularly the PE group of proteins in the context of 'virulence' determinants and outcome of tuberculosis disease. Additionally, we have discussed about the roles of these proteins on host-pathogen-interaction and how some of these genes can be targeted which may help us in designing effective anti-TB therapeutics.

Objective: Heart failure (HF) causes structural and functional changes in the heart, with the pyroptosis-mediated inflammatory response as the core link in HF pathogenesis. E3 ubiquitin ligases participate in cardiovascular disease progression. Here, we explored the underlying molecular mechanisms of E3 ubiquitin ligase Smurf1 in governing HF.

Methods: HF rat/H9C2 cell models were established by doxorubicin intraperitoneal injections/hypoxia-reoxygenation (H/R), and treated with Smurf1 siRNA and oe-TRIB2 lentivirus plasmids or the NF-κB pathway inhibitor PDTC/si-smurf1, si-TRIB2, protease inhibitor MG132, or lysosomal inhibitor NH4Cl. The cardiac function/cardiac tissue pathological changes/fibrosis in HF rats were evaluated by echocardiography/H&E and Masson staining. GSDMD-N expression was determined by immunohistochemistry. Cell viability/lactate dehydrogenase (LDH) activity/IL-1β and IL-18 levels were measured by CCK-8/LDH kit/ELISA. The interaction between TRIB2 and Smurf1/TRIB2 ubiquitination levels was assessed by co-immunoprecipitation assay. The expression levels of Smurf1 and TRIB2 messenger RNA (mRNA) were determined by RT-qPCR. Levels of Smurf1/TRIB2/the NF-κB pathway-related factors/pyroptosis-related factors and TRIB2 mRNA were determined by Western blot/RT-qPCR.

Results: Smurf1 was highly expressed in H/R-induced H9C2 cells/HF rats, while its knockdown up-regulated TRIB2 and repressed the NF-κB pathway, reduced cardiomyocyte pyroptosis, and attenuated HF. Mechanistically, Smurf1 promoted TRIB2 degradation through an ubiquitin-dependent manner and activated the NF-κB pathway under H/R conditions. TRIB2 silencing annulled Smurf1 knockdown-regulated NF-κB pathway and cardiomyocyte pyroptosis. TRIB2 overexpression inactivated the NF-κB pathway and reduced cardiomyocyte pyroptosis, thus retarding HF.

Conclusion: Smurf1 was highly expressed in HF rats, which promoted TRIB2 ubiquitination degradation and activated the NF-κB pathway, thereby promoting cardiomyocyte pyroptosis in HF rats.

Aluminum salt-based adjuvants like alum, alhydrogel and Adju-Phos are by far the most favored clinically approved vaccine adjuvants. They have demonstrated excellent safety profile and currently used in vaccines against diphtheria, tetanus, pertussis, hepatitis B, anthrax etc. These vaccinations cause minimal side effects like local inflammation at the injection site. Aluminum salt-based adjuvants primarily stimulate CD4⁺ T cells and B cell mediated Th2 immune response leading to generate a robust antibody response. In this review article, we have compiled the role of physio-chemical role of the two commonly used aluminum salt-based adjuvants alhydrogel and Adju-Phos, and the effect of surface properties, buffer composition, and adjuvant dosage on the immune response. After being studied for almost a century, researchers have come up with various mechanism by which these aluminum adjuvants activate the immune system. Firstly, we have covered the initial works of Glenny and his "repository effect" which paved the work for his successors to explore the involvement of cytokines, chemokines, recruitment of innate immune cells, enhanced antigen uptake by antigen presenting cells, and formation of NLRP3 inflammasome complex in mediating the immune response. It has been reported that aluminum adjuvants activate multiple immunological pathways which synergistically activates the immune system. We later discuss the recent developments in nanotechnology-based preparations of next generation aluminum based adjuvants which has enabled precise size control and morphology of the traditional aluminum adjuvants thereby manipulating the immune response as per our desire.

TGF-β is a pivotal cytokine that orchestrates various aspects of cancer progression, including tumor growth, metastasis, and immune evasion. In this review, we present a comprehensive overview of the multifaceted role of transforming growth factor β (TGF-β) in cancer biology, focusing on its intricate interactions with monocytes and macrophages within the tumor microenvironment (TME). We specifically discuss how TGF-β modulates monocyte and macrophage activities, leading to immunosuppression and tumor progression. We conclude with the current translational and clinical efforts targeting TGF-β, recognizing the promising role of this strategy in immunooncology.

Because of numerous stress signals, intracellular protein complexes are called inflammasomes. They function as catalysts for the proteolytic transformation of pro-interleukin into the active form of interleukin. Inflammasomes can promote a type of cell death process known as pyroptosis. The NLRP3 inflammasome, comprised of the NLRP3 protein, procaspase-1, and ASC, tightly regulates inflammation. The NLRP3 inflammasome is activated by a variety of stimuli, and several molecular and cellular events, such as ion influx, mitochondrial dysfunction, reactive oxygen species production, and lysosomal damage have been shown to trigger its activation. Inflammation plays a major role in almost all types of human diseases. The NLRP3 inflammasome has been the most widely studied and plays an important pathogenic role in various inflammatory pathologies. This review briefly presents the basic features of NLRP3 inflammasome and their mechanisms of activation and regulation. In addition, recent studies report the role of NLRP3 inflammasome in several diseases have been summarized.

In recent years, mostly spanning the past decade, the concept of immunometabolism has ushered with a novel perspective on carcinogenesis, tumor progression, and tumor response to therapy. It has become clear that the metabolic state of immune cells plays a significant role in shaping their antitumor or protumor activities within the cancer microenvironment. Consequently, the examination of tumor metabolic heterogeneity, including an exploration of immunometabolism, proves indispensable for enhancing prognostic tools and advancing the quest for personalized treatments. Here we have delved into how metabolic reprogramming profoundly influences the acquisition and maintenance of functional states, spanning from effector and cytotoxic profiles to regulatory and immunosuppressive phenotypes in both innate and adaptive immunity. These alterations wield considerable influence over tumor evolution and affect the outcome of cancer. Furthermore, we explore some of the cellular signaling mechanisms that underpin the metabolic and phenotypic flexibility of immune cells in response to external stimuli.

This study aimed to explore the critical role of FUNDC1 on epithelial cells in model of asthma. Patients with asthma and normal healthy volunteers were obtained from our hospital. The serum of FUNDC1 mRNA expression was down-regulated in patients with asthma. Meanwhile, the serum of FUNDC1 mRNA expression was positive correlation with IgE and anti-HDM IgE protein. FUNDC1 expression in lung tissue of mice model was decreased in mice model of asthma. Sh-FUNDC1 enhanced asthma in mice model of asthma. FUNDC1 up-regulation reduced IL-4, IL-5, IL-10 and IL-13 activity levels in vitro model of asthma.FUNDC1 down-regulation promoted IL-4, IL-5, IL-10 and IL-13 activity levels in vitro model of asthma. FUNDC1 reduced ferroptosis of epithelial cells in model of asthma through the inhibition of mitochondrial damage. FUNDC1 induced FBXL2 and AR protein expression in model of asthma. FUNDC1 interlinked with FBXL2 is modified by SUMO1 at K136. FBXL2, ASN-205, GLN-204, ARG-235, and GLN-237 form hydrogen bonds with FUNDC1's ASP-15, ASP-16, GLU-25, and ARG-29, with lengths of 2.3, 3.1, 2.9, 2.3, and 2.9 Å, respectively. The induction of FBXL2 reduced the effects of Sh-FUNDC1 on asthma in mice model of asthma. The inhibition of AR reduced the effects of Sh-FUNDC1 on asthma in mice model of asthma Overall, FUNDC1 prevents ferroptosis of airway epithelial cells of asthma through FBXL2/AR/GPX4 signaling pathway of SUMO1 at K136. FUNDC1 might benefit the treatment of asthma or other pulmonary disease.

Host immunity helps the body to fight against COVID-19. Single-cell transcriptomics has provided the scope of investigating cellular and molecular underpinnings of host immune response against SARS-CoV-2 infection at high resolution. In this review, we have systematically described the virus-induced dysregulation of relative abundance as well as molecular behavior of each innate and adaptive immune cell type and cell state during COVID-19 infection and for different vaccinations, based on single-cell studies published in last three-four years. Identification and characterization of these disease-associated specific cell populations might help to design better, efficient, and targeted therapeutic avenues.

Preventive vaccination is a crucial strategy for controlling and preventing infectious diseases, offering both effectiveness and cost-efficiency. However, despite the widespread success of vaccination programs, there are still certain population groups who struggle to mount adequate responses to immunization. These at-risk groups include but are not restricted to the elderly, overweight individuals, individuals with chronic infections and cancer patients. All of these groups are characterized by persistent chronic inflammation. Recent studies have demonstrated that one of the key players in immune regulation and the promotion of chronic inflammation are myeloid-derived suppressor cells (MDSCs). These cells possess a wide range of immunosuppressive mechanisms and are able to dampen immune responses in both antigen-specific and antigen-nonspecific manner, thus contributing to the establishment and maintenance of an inflammatory environment. Given their pivotal role in immune modulation, there is growing interest in understanding how MDSCs may influence the efficacy of vaccines, particularly in vulnerable populations. In this narrative review, we discuss whether MDSCs are able to regulate vaccine-induced immunity and whether their suppression can potentially enhance vaccine efficacy in vulnerable populations.

Studies in murine experimental models have made significant contributions to the understanding of asthma pathophysiology and the discovery of innovative therapeutic approaches. Nonetheless, there is a plethora of options available for selecting mouse strains, sensitization methods, challenge routes and doses, as well as approaches to evaluating host response in murine asthma model protocols. Due to the diversity of models employed, comparing results across different studies proves exceedingly challenging. The study conducted a search of pertinent PubMed articles from 2022 to April 15th, 2024. After relevant publications had been selected, the characteristics of each study were extracted, including animal strains, animal sex, sensitization methods, challenge methods, and reported outcome measures. The modeling parameters of Ovalbumin (OVA)-induced asthma model, and House Dust Mite-induced asthma model were analyzed. Additionally, we extracted data on the dose of OVA sensitization, alum administration, challenge OVA dose, and alum/sensitization OVA ratio from seven included studies. Subsequently, we conducted an analysis to determine the correlation between each of these factors and the lung resistance index (RI). This study presents an overview of the current mouse asthma models, offering valuable methodological guidance for researchers. Furthermore, this study highlights that certain parameters like sensitization dose, challenge dose, and so on, exert specific effects on the asthma lung resistance. However, there is a lack of standardized criteria and guidelines in this regard. The effects and underlying mechanisms of parameters on asthma responses remain unclear, necessitating further investigation into model parameters.