Current research in immunology最新文献

Advances in transcriptomics and proteomics have revealed that different life-cycle stages of the malaria parasite, Plasmodium, share antigens, thus allowing for the possibility of eliciting immunity to a parasite life-cycle stage that has not been experienced before. Using the Plasmodium chabaudi (AS strain) model of malaria in mice, we investigated how isolated exposure to blood-stage infection, bypassing a liver-stage infection, yields significant protection to sporozoite challenge resulting in lower liver parasite burdens. Antibodies are the main immune driver of this protection. Antibodies induced by blood-stage infection recognise proteins on the surface of sporozoites and can impair sporozoite gliding motility in vitro, suggesting a possible function in vivo. Furthermore, mice lacking B cells and/or secreted antibodies are not protected against a sporozoite challenge in mice that had a previous blood-stage infection. Conversely, effector CD4⁺ and CD8⁺ T cells do not seem to play a role in protection from sporozoite challenge of mice previously exposed only to the blood stages of P. chabaudi. The protective response against pre-erythrocytic stages can be induced by infections initiated by serially passaged blood-stage parasites as well as recently mosquito transmitted parasites and is effective against a different strain of P. chabaudi (CB strain), but not against another rodent malaria species, P. yoelii. The possibility to induce protective cross-stage antibodies advocates the need to consider both stage-specific and cross-stage immune responses to malaria, as natural infection elicits exposure to all life-cycle stages. Future investigation into these cross-stage antibodies allows the opportunity for candidate antigens to contribute to malaria vaccine development.

In physiological conditions, the human gut contains more immune cells than the rest of the body, but no overt tissue damage occurs, because several regulatory mechanisms control the activity of such cells thus preventing excessive and detrimental responses. One such mechanism relies on the action of transforming growth factor (TGF)-β1, a cytokine that targets both epithelial cells and many immune cell types. Loss of TGF-β1 function leads to intestinal pathology in both mice and humans. For instance, disruption of TGF-β1 signaling characterizes the destructive immune-inflammatory response in patients with Crohn’s disease and patients with ulcerative colitis, the major human inflammatory bowel disease (IBD) entities. In these pathologies, the defective TGF-β1-mediated anti-inflammatory response is associated with elevated intestinal levels of Smad7, an antagonist of TGF-β1 signaling. Consistently, knockdown of Smad7 restores TGF-β1 function thereby attenuating intestinal inflammation in patients with IBD as well as in mice with IBD-like colitis. Up-regulation of Smad7 and reduced TGF-β1 signaling occurs also in necrotizing enterocolitis, environmental enteropathy, refractory celiac disease, and cytomegalovirus-induced colitis. In this article, we review the available data supporting the pathogenic role of Smad7 in the gastrointestinal tract and discuss whether and how targeting Smad7 can help attenuate detrimental immuno-inflammatory responses in the gut.

Concerns for the long-term effects of COVID-19 infection have grown due to frequently reported persisting symptoms that can affect multiple systems for longer than 4 weeks after initial infection, a condition known as long-COVID-19 or post-acute COVID-19 syndrome (PACS). Even nonhospitalized survivors have an elevated risk for the development of thromboinflammatory-associated events, such as ischemic stroke and heart failure, pulmonary embolism and deep vein thrombosis. Recent findings point to the persistence of many mechanisms of hypercoagulability identified to be associated with disease severity and mortality in the acute phase of the disease, such as sustained inflammation and endotheliopathy, accompanied by abnormal fibrin generation and impaired fibrinolysis. Platelets seem to be central to the sustained hypercoagulable state, displaying hyperreactivity to stimuli and increased adhesive capacity. Platelets also contribute to elevated levels of thromboinflammatory mediators and pro-coagulant extracellular vesicles in individuals with ongoing PACS. Despite new advances in the understanding of mechanisms sustaining thromboinflammation in PACS, little is known about what triggers this persistence. In this graphical review, we provide a schematic representation of the known mechanisms and consequences of persisting thromboinflammation in COVID-19 survivors and summarize the hypothesized triggers maintaining this prothrombotic state.

Despite improvements in anti-Human Leucocyte Antigens antibody detection, identification, and characterization offer a better in peri-operative management techniques, antibodies remain a serious cause of morbidity and mortality for patients both before and after organ transplantation. Hyperimmune patients are disadvantaged by having to wait longer to receive an organ from a suitably matched donor. They could benefit from desensitization protocols in both pre- and post-transplantation period. Clinical studies are underway to highlight which best desensitization strategies could be assure the best outcome in both heart and kidney transplantation. Although most clinical evidence about desensitization strategies by using anti-CD20 monoclonal antibodies, proteasome inhibitors, anti-CD38 monoclonal antibodies, interleukin-6 blockade, cysteine protease and complement inhibitors, comes from kidney transplantation studies, many of the debated novel concepts can be easily applied to desensitization also in heart transplantation.

Here, we discuss the candidates and recipients’ management by using most common standard of care and novel therapeutics, desensitization endpoints, and strategies for future studies.

Tissue-resident memory T cells (Trm) are a sub-population of memory T cells that reside in skin tissue. Recent studies have revealed potential role of Trm in the reoccurrence of psoriasis, as these cells tend to be profusely infiltrated in the lesions observed during psoriasis relapse. Trm can be classified into CD8⁺ Trm cells that are distributed mainly in the epidermis and CD4⁺ Trm cells in the dermis. CD8⁺ Trm is derived from circulating memory T cells and CD49a⁻CD8⁺ Trm takes a crucial role in psoriasis relapse. In contrast, CD4⁺ Trm may originate from exTh17 cells and exTreg cells emerging from the inflammatory process. Since IL-23 can activate Trm, neutralizing antibodies against IL-23 are suggested to be more effective in clinical treatment. This review will focus on Trm cells in psoriasis relapsed lesions to reveal their mechanisms in the pathogenesis, relapse and transformation of psoriasis.

Nanoparticles (NPs) physicochemical properties, such as size, shape, surface chemistry, charge, etc., play a critical role in biological systems interactions, which include NPs' cellular uptake, trafficking, activation, and toxicity. Although nano-bio interactions are multifaceted and complex, their assessment is essential for future therapeutic and diagnostic use since being carriers that deliver specific molecules (i.e., active pharmaceutical ingredients and imaging agents) in intracellular sites. The journey of NPs begins by reaching the plasma membrane and entering the cell mainly through endocytosis. After vesicles pinch off the cell membrane, the intracellular trafficking is mediated by a network of cellular endosomes which direct NPs to the different cellular components. Otherwise, NPs or their contents are released into the cytoplasm. In both cases, NPs can pass undetected or be recognized by the cell leading to a pro or anti-inflammatory response. Indeed, the cell response mostly depends on cell type and NPs physicochemical properties. The principal mechanism by which NPs activate the cell response is RONS production. Other mechanism includes signaling pathways modulation related to metabolic and enzymatic reactions, cell transduction, and immune modulation. Hence, the underlying mechanisms of cellular and subcellular interactions in vitro should be performed to provide insights into NPs' effect. This information helps us to improve their synthesis and design to maximize the clinical benefits while minimizing side effects. Most in vitro tests to evaluate NPs' effect in cells were developed focusing on cell dysfunctions, cytotoxicity, genotoxicity, immunogenicity, and cell death.

The research interest of the scientific community in biofilm-forming microorganisms is growing due to the problems caused by their infections affecting humans and animals, mainly because of the difficulty of the host immune system in eradicating these microbial complex communities and the increasing antimicrobial resistance rates worldwide. This review describes the virulence factors and their interaction with the microbial communities of four well-known and highly biofilm-forming pathogens, more exactly, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus spp., and Candida spp. The innate and adaptive immune responses caused by the infection with these microorganisms and their evasion to the host immune system by biofilm formation are discussed in the present work. The relevance of the differences in the expression of certain virulence factors and the immune response in biofilm-associated infections when compared to planktonic infections is usually described as the biofilm architecture protects the pathogen and alters the host immune responses, here we extensively discussed these mechanisms.

Purpose of review

Asthma is a common heterogeneous group of chronic inflammatory diseases with different pathological phenotypes classified based on the various clinical, physiological and immunobiological profiles of patients. Despite similar clinical symptoms, asthmatic patients may respond differently to treatment. Hence, asthma research is becoming more focused on deciphering the molecular and cellular pathways driving the different asthma endotypes. This review focuses on the role of inflammasome activation as one important mechanism reported in the pathogenesis of severe steroid resistant asthma (SSRA), a Th2-low asthma endotype. Although SSRA represents around 5–10% of asthmatic patients, it is responsible for the majority of asthma morbidity and more than 50% of asthma associated healthcare costs with clear unmet need. Therefore, deciphering the role of the inflammasome in SSRA pathogenesis, particularly in relation to neutrophil chemotaxis to the lungs, provides a novel target for therapy.

Recent findings

The literature highlighted several activators of inflammasomes that are elevated during SSRA and result in the release of proinflammatory mediators, mainly IL-1β and IL-18, through different signaling pathways. Consequently, the expression of NLRP3 and IL-1β is shown to be positively correlated with neutrophil recruitment and negatively correlated with airflow obstruction. Furthermore, exaggerated NLRP3 inflammasome/IL-1β activation is reported to be associated with glucocorticoid resistance.

Summary

In this review, we summarized the reported literature on the activators of the inflammasome during SSRA, the role of IL-1β and IL-18 in SSRA pathogenesis, and the pathways by which inflammasome activation contributes to steroid resistance. Finally, our review shed light on the different levels to target inflammasome involvement in an attempt to ameliorate the serious outcomes of SSRA.

This study tested the hypothesis that high frequencies of natural killer (NK) cells are protective against symptomatic SARS-CoV-2 infection. Samples were utilized from the COVID-19 Health Action Response for Marines study, a prospective, observational study of SARS-CoV-2 infection in which participants were enrolled prior to infection and then serially monitored for development of symptomatic or asymptomatic infection. Frequencies and phenotypes of NK cells (CD3⁻CD14⁻CD19⁻CD56⁺) were assessed by flow cytometry. Individuals that developed asymptomatic infections were found to have higher pre-infection frequencies of total NK cells compared to symptomatic individuals (10.61% [SD 4.5] vs 8.33% [SD 4.6], p = 0.011). Circulating total NK cells decreased over the course of infection, reaching a nadir at 4 weeks, while immature NK cells increased, a finding confirmed by multidimensional reduction analysis. These results indicate that NK cells likely play a key role in controlling the severity of clinical illness in individuals infected with SARS-CoV-2.

The immune system has a variety of potential effects on a tumor microenvironment and the course of chemotherapy may vary according to that. Anticancer treatments can encourage the release of unwanted signals from senescent tumor cells or the removal of immune-suppressive cells, which can lead to immune system activation. Hence, by inducing an immunological response and conversely making cancer cells more vulnerable to immune attack, chemotherapeutic agents can destroy cancer cells. Furthermore, chemotherapy can activate anticancer immune effectors directly or indirectly by thwarting immunosuppressive pathways. Therefore, in this review, we discuss how chemotherapeutic agents take part in immunomodulation and the molecular mechanisms underlying them. We also focus on the importance of carefully addressing the conflicting effects of chemotherapy on immune responses when developing successful combination treatments based on chemotherapy and immune modulators.