Journal of Immunology Research最新文献

Research on long-term follow-up in individuals who have recovered from coronavirus disease-19 (COVID-19) would yield insights regarding their immunity status and identify those who need booster vaccinations. This study evaluated the longevity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular and humoral memory responses, as well as T cell effector functionalities, at 1-2 months (n = 40), 8-9 months (n = 40), and 12 months/1 year (n = 27) following recovery from SARS-CoV-2 infection. CTL response by enzyme-linked immunospot (ELISPOT); levels of cytokine by Bio-Plex, natural killer (NK), CD4+ helper, and CD8+ cytotoxic T cell functionalities using flow cytometry; anti-SARS-CoV-2 IgG by ELISA; and levels of neutralizing antibodies (NAbs) by surrogate virus NAb assay were assessed. The levels of SARS-CoV-2-specific IgG and NAb at 1-2 and 8-9 months postrecovery were hand in hand and appeared declining. SARS-CoV-2-specific B, memory B and plasma cells, and T cells sustained up to 8-9 months. Increased expression of CD107a/IFN-γ by NK cells and cytotoxic T cells at 8-9 months could be indicative of SARS-CoV-2-specific effector functions. Recovered individuals with positive and negative IgG antibody status displayed T cell response up to 1 year and 8-9 months, respectively, emphasizing the durabilty of effector immunity up to 8-9 months regardless of IgG antibody status. Overall, the recovered individuals exhibited robust immunological memory, sustained T cell response with effector functionality against SARS-CoV-2 that persists for at least 8-9 months.

Leishmaniasis is a group of parasitic diseases whose etiological agent is the protozoa Leishmania. These diseases afflict impoverished populations in tropical and subtropical regions and affect wild and domestic animals. Canine leishmaniasis is a global disease mostly caused by L. infantum. Dogs are recognized as a good reservoir since harbor the infection long before developing the disease, facilitating parasite transmission. Furthermore, there is growing evidence that dogs may also be the reservoir of the American Leishmania spp. as L. amazonensis. The innate immune response is the first defense line against pathogens, which includes natural killer (NK) and dendritic cells (DCs). By recognizing and ultimately destroying infected cells, and by secreting immune mediators that favor inflammatory microenvironments, NK cells take the lead in the infectious process. When interacting with Leishmania parasites, DCs become activated and play a key role in driving the host immune response. While activated DCs can modulate NK cell activity, Leishmania parasites can directly activate NK cells by interacting with innate immune receptors. Once activated, NK cells can engage in a bidirectional interplay with DCs. However, the complexity of these interactions during Leishmania infection makes it challenging to fully understand the underlying processes. To further explore this, the present study investigated the dynamic interplay established between monocyte-derived DCs (moDCs) and putative NK (pNK) cells of dogs during Leishmania infection. Findings indicate that the crosstalk between moDCs exposed to L. infantum or L. amazonensis and pNK cells enhances chemokine upregulation, potentially attracting other leukocytes to the site of infection. pNK cells activated by L. infantum infected DCs upregulate IL-10, which can lead to a regulatory immune response while moDCs exposed to L. amazonensis induced pNK cells to overexpress IFN-γ and IL-13, favoring a mix of pro- and anti-inflammatory response. In addition, parasite-derived extracellular vesicles (EVs) can modulate the host immune response by stimulating the upregulation of anti-inflammatory cytokines and perforin release, which may impact infection outcomes. Thus, Leishmania and parasitic EVs can influence the bidirectional interplay between canine NK cells and DCs.

Amino acid metabolism in T cells determines the therapeutic efficacy of T-cell-targeting drugs. To assess the direction of amino acid metabolism in T cells and construct related knowledge structure, we performed a bibliometric analysis aiming at amino acid metabolism in T cells utilizing studies publicized in recent 15 years. Three hundred thirty-seven related studies were downloaded from the Web of Science Core Collection (WoSCC), and the information on countries, institutes, and authors was collected and analyzed. In addition, the present research status and future trends were explored according to the results yielded from the analysis of cited references and keywords. This study revealed that publications regarding amino acid metabolism in T cells gradually increased each year. The USA is the top producer and most influential country in this field. Recent research has focused on the correlation between the metabolism of several amino acids and regulatory T cells (Tregs) and CD8⁺ T cells. Overall, this research offers a comprehensive exhibition on the field of amino acid metabolism in T cells, which will help researchers to study this domain more effectively and intuitively.

In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has made groundbreaking progress in the treatment of various cancer types, particularly hematological malignancies. In the meantime, various preclinical and clinical studies have extensively explored dual-target CAR-T therapies which can be designed to recognize two antigens simultaneously based on the immunophenotype of tumor cells. Compared with single-target CAR-T approach, dual-target CAR-T therapies demonstrate varying degrees of superior antitumor CAR effects, prevent antigen escape and relapse, reduce on-target off-tumor effects, and ensure durable responses in different types of cancer. These advantages highlight the potential future prospects in this field, showing varying degrees of advancement in preclinical and clinical studies. Herein, we aimed to review different dual-target CAR-T studies conducted on a wide range of tumor models, summarizing the selection of target combinations, the efficacy and safety demonstrated in preclinical and clinical settings, the existing limitations, and the potential future directions of this promising therapeutic strategy.

Inflammation is a critical response of the immune system to infection or injury, serving to repair and restore tissue homeostasis. While acute inflammation generally protects against harmful stimuli, prolonged and chronic inflammation have detrimental effects and disrupts tissue homeostasis. Due to the complex and multifactorial etiology of chronic inflammation, effective treatment remains elusive. We found that piperlongumine (PL)-18, a di-hydroxy derivative of PL from long pepper, inhibits the nuclear factor kappa B (NF-kB), a master transcription factor of numerous components of the inflammatory response. NF-kB was inhibited by PL-18 in two human cell-lines, L428 and A549, by preventing the nuclear translocation of p65 NF-kB. We also found that IκB kinase (IKK) was degraded in the presence of PL-18. Furthermore, PL-18 inhibited the production of proinflammatory cytokines expressed by L428, a cell line with a constitutive active NF-kB. Altogether, our results suggest that PL-18 is a molecule of interest to be further developed to treat persistent infections with severe inflammation.

The body's immune response plays a critical role in defending against external or foreign antigens while also preserving tolerance to self-antigens. This equilibrium, referred to as immune homeostasis, is paramount for overall health. The regulatory mechanisms governing the maintenance of this delicate immune balance are notably complex. It is currently accepted that immune tolerance is a dynamic outcome regulated by multiple factors, including central and peripheral mechanisms. Its induction or elimination plays a significant role in autoimmune diseases, organ transplantation, and cancer therapy, markedly impacting various major diseases in modern clinical practice. Overall, our current understanding of immune tolerance is still very limited. In this review article, we summarized the main mechanisms that have been known to mediate immune tolerance so far, including endogenous immune tolerance, adaptive immune tolerance, other immune tolerance mechanisms, and the homeostasis of immune tolerance, identified the key factors that regulate immune tolerance, and provided new clues for immune system recovery in many autoimmune diseases, organ transplantation, and tumor therapy.

Antimicrobial peptides (AMPs) are crucial components of the innate immune system in all living organisms, playing a vital role in the body's defense against diseases and infections. The immune system's primary functions include preventing disease-causing agents from entering the body and eliminating them without causing harm. These peptides exhibit broad-spectrum activity against bacteria, viruses, fungi, parasites, and cancer cells. They are secreted by innate and epithelial cells and contribute to host defense by inducing cellular activities such as cell migration, proliferation, differentiation, cytokine production, angiogenesis, and wound healing. In response to the growing challenge of bacterial resistance to antimicrobial agents, alternative drugs and new antibacterial molecules are being explored. In a previous study, NET AMPs were synthesized and their antimicrobial effects were determined. The current study extends this work by assessing the effects of these peptides on the immune system through cell culture experiments and ELISA. Specifically, the study investigated how different concentrations of these peptides influence the secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in mouse macrophages. Among the synthesized peptides, NET1 and NET2 demonstrated low cytotoxicity in TIB-71 RAW 264.7 macrophages. These peptides induced an anti-inflammatory response and reduced IL-6 expression in the absence of LPS stimulation, while simultaneously increasing IFN-γ and TNF-α secretion. These findings suggest that NET1 and NET2 peptides possess both anti-inflammatory and pro-inflammatory properties, highlighting their potential role in modulating immune responses.

Acute liver failure (ALF) is a fulminant clinical syndrome that usually leads to multiple organ failure and high mortality. Macrophages play a crucial role in the initiation, development, and recovery of ALF. Targeting macrophages through immunotherapy holds significant promise as a therapeutic strategy. These cells exhibit remarkable plasticity, enabling them to differentiate into various subtypes based on changes in their surrounding microenvironment. M1-type macrophages are associated with a pro-inflammatory phenotype and primarily rely predominantly on glycolysis. In contrast, M2-type macrophages, which are characterized by anti-inflammatory phenotype, predominantly obtain their energy from oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO). Shifting macrophage metabolism from glycolysis to OXPHOS inhibits M1 macrophage activation and promotes M2 macrophage activation, thereby exerting anti-inflammatory and reparative effects. This study elucidates the relationship between macrophage activation and glucose metabolism reprograming from an immunometabolism perspective. A comprehensive literature review revealed that several signaling pathways may regulate macrophage polarization through energy metabolism, including phosphatidyl-inositol 3-kinase/protein kinase B (PI3K/AKT), mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1α (HIF-1α), nuclear factor-κB (NF-κB), and AMP-activated protein kinase (AMPK), which exhibit crosstalk with one another. Additionally, we systematically reviewed several traditional Chinese medicine (TCM) monomers that can modulate glucose metabolism reprograming and influence the polarization states of M1 and M2 macrophages. This review aimed to provide valuable insights that could contribute to the development of new therapies or drugs for ALF.

Background: Manual therapy (MT) has been widely used in China to treat local tissue inflammation for a long time. However, there is a lack of scientific evidence for using MT in anti-inflammatory therapy, and its anti-inflammatory mechanism needs further clarification. Methods: We utilized MT to treat cardiotoxin (CTX) injury-induced skeletal muscle inflammation in C57BL6/J mice. We analyzed the underlying mechanism by integrating single-cell RNA sequencing (scRNA-seq) with molecular techniques. Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were used to assess skeletal muscle inflammation and muscle fiber cross-sectional area (CSA). scRNA-seq, immunofluorescence, and western blot were performed to determine cellular and molecular outcome changes. Results: Compared with CTX injury-induced skeletal muscle inflammatory mice, MT intervention significantly reduced proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) expression levels; scRNA-seq detected that neutrophil numbers and activity were maximum proportions increased in injured skeletal muscle among macrophage, T cells, B cells, endothelial cells, fast muscle cells, fibroblasts, and skeletal muscle satellite cells; and S100A9 gene expression was supreme in neutrophils. However, after treatment with MT, S100A9 protein expression and the numbers and activity of Ly6g+/Mpo+ neutrophils were significantly inhibited, thus reducing the inflammatory cytokine levels and exerting an anti-inflammatory effect by early clearing neutrophils. Conclusion: MT can mitigate localized inflammation induced by injured skeletal muscle, achieved by decreasing S100A9 protein expression and clearing neutrophils in mice, which may help advance therapeutic strategies for skeletal muscle localized inflammation.