Journal of Innate Immunity最新文献

Introduction: Hepatitis B virus (HBV)-related liver diseases, including hepatitis, cirrhosis, and liver failure, seriously threaten human lives and health worldwide. Innate and adaptive immune cells are all thought to participate in HBV-related diseases. However, there is a lack of information on the comprehensive landscape of the immune microenvironment.

Methods: In this study, single-cell ribonucleic acid sequencing was performed on liver samples obtained from patients diagnosed with hepatitis, cirrhosis, and acute-on-chronic liver failure, which were caused by HBV. Trajectory analysis was performed to analyze the evolution of cell subsets, and branch expression analysis modeling was applied to visualize the changes in gene expression during evolution.

Results: Finally, there was a significant increase in adaptive immune cells in the hepatitis and cirrhosis groups, whereas more innate immune cells were observed in the liver failure group. Furthermore, we found that monocytes underwent remarkable transcriptomic changes into FABP5+ macrophages, promoting the degranulation and chemotaxis of neutrophils through RESISTIN signaling, and LGMN+ macrophages, with the sequential activation of antigen presentation and defense to pathogens through SPP1 signaling.

Conclusion: Macrophages were revealed as central to the progression of acute-on-chronic liver failure as they regulated the activation or inhibition of other immune cells, which could help in developing an effective novel therapy.

Introduction: Neutrophils are key players in the hyperinflammatory response during SARS-CoV-2 infection. The cytosolic proliferating cell nuclear antigen (PCNA) is a scaffolding protein highly dependent on the microenvironment status and known to interact with numerous proteins that regulate neutrophil functions. This study aimed to examine the cytosolic protein content and PCNA interactome in neutrophils from COVID-19 patients.

Methods: Proteomic analyses were performed on neutrophil cytosols from healthy donors and patients with severe or critical COVID-19. In vitro approaches were used to explore the biological significance of the COVID-19-specific PCNA interactome.

Results: Neutrophil cytosol analysis revealed a strong interferon (IFN) protein signature, with variations according to disease severity. Interactome analysis identified associations of PCNA with proteins involved in interferon signaling, cytoskeletal organization, and neutrophil extracellular trap (NET) formation, such as protein arginine deiminase type-4 (PADI4) and histone H3, particularly in critical patients. Functional studies of interferon signaling showed that T2AA, a PCNA scaffold inhibitor, downregulated IFN-related genes, including STAT1, MX1, IFIT1, and IFIT2 in neutrophils. Additionally, T2AA specifically inhibited the secretion of CXCL10, an IFN-dependent cytokine. PCNA was also found to interact with key effector proteins implicated in NET formation, such as histone H3, especially in critical COVID-19 cases.

Conclusion: The analysis of the PCNA interactome has unveiled new protein partners that enhance the interferon pathway, thereby modulating immune responses and contributing to hyperinflammation in COVID-19. These findings provide valuable insights into interferon dysregulation in other immune-related conditions.

Introduction: Neutrophils are key players in the hyperinflammatory response during SARS-CoV-2 infection. The cytosolic proliferating cell nuclear antigen (PCNA) is a scaffolding protein highly dependent on the microenvironment status and known to interact with numerous proteins that regulate neutrophil functions. This study aimed to examine the cytosolic protein content and PCNA interactome in neutrophils from COVID-19 patients.

Methods: Proteomic analyses were performed on neutrophil cytosols from healthy donors and patients with severe or critical COVID-19. In vitro approaches were used to explore the biological significance of the COVID-19-specific PCNA interactome.

Results: Neutrophil cytosol analysis revealed a strong interferon (IFN) protein signature, with variations according to disease severity. Interactome analysis identified associations of PCNA with proteins involved in interferon signaling, cytoskeletal organization, and neutrophil extracellular trap (NET) formation, such as protein argi

Introduction: Species of the ananassae subgroup of Drosophilidae are highly resistant to parasitoid wasp infections. We have previously shown that the genes encoding cytolethal distending toxin B (CdtB) and the apoptosis inducing protein of 56 kDa (AIP56) were horizontally transferred to these fly species from prokaryotes and are now instrumental in the anti-parasitoid immune defense of Drosophila ananassae. Here we describe a new family of genes, which encode proteins with hemolysin E domains, heretofore only identified in prokaryotes. Hemolysin E proteins are pore-forming toxins, important virulence factors of bacteria.

Methods: Bioinformatical, transcriptional, and protein expressional studies were used.

Results: The hemolysin E-like genes have a scattered distribution among the genomes of species belonging to several different monophyletic lineages in the family Drosophilidae. We detected structural homology with the bacterial Hemolysin E toxins and showed that the origin of the D. ananassae hemolysin E-like genes (hl1-38) is consistent with prokaryotic horizontal gene transfer. These genes encode humoral factors, secreted into the hemolymph by the fat body and hemocytes. Their expression is induced solely by parasitoid infection and the proteins bind to the developing parasitoids.

Conclusions: Hemolysin E-like proteins acquired by horizontal gene transfer and expressed by the primary immune organs may contribute to the elimination of parasitoids, as novel humoral factors in Drosophila innate immunity.

Introduction: Dendritic cells (DCs) are crucial in immune responses; however, the role of DCs in trauma patients remains poorly understood. Therefore, this study aimed to investigate the frequencies and functions of two major DC subsets in trauma patients: plasmacytoid DCs (pDCs) and conventional DCs (cDCs).

Methods: This study included 25 trauma patients and 40 healthy controls. Using flow cytometry, the frequencies, cytokine production (IFN-α, TNF-α, IL-12), and expression of co-stimulatory (CD86) and co-inhibitory (CD274) markers were analyzed in the DC subsets. The relationship between CD274+ pDCs and the Injury Severity Score (ISS) was also evaluated. Additionally, in vitro experiments were conducted using proinflammatory cytokine stimulation and blocking antibodies to assess their effects on DC activation markers.

Results: Trauma patients showed decreased percentages and absolute numbers of pDCs, while cDC levels remained unchanged. Cytokine production was impaired, with reduced IFN-α and TNF-α from pDCs and IL-12 from cDCs. CD86+ and CD274+ expressions were increased in pDCs but decreased in cDCs, with CD274+ pDCs positively correlating with ISS. In vitro studies revealed that proinflammatory cytokine exposure enhanced activation markers, peaking at 72 h; this observation was reversed by blocking antibodies.

Conclusion: This study demonstrates that trauma induces both numerical and functional deficiencies in circulating pDCs despite increased activation marker expression. The correlation between CD274+ pDCs and trauma severity, along with the temporal dynamics of cytokine-induced activation, suggests a complex role for pDCs in post-traumatic immune responses. These findings provide new insights for developing targeted therapies for trauma-related immune complications.

Background: Toll-like receptors (TLRs) are one of the first pattern recognition receptors found in the innate immune system. The TLR family has 12 members (TLR1-TLR9, TLR11-TLR13) in mice and 10 members (TLR1-TLR10) in humans, with TLR10 being the latest identified.

Summary: Considerable research has been performed on TLRs; however, TLR10 is known as an orphan receptor for the lack of information on its signalling, role, and ligands. Even though there are recent studies pointing towards the potential TLR10 ligands, their function and signalling pathway are yet to be determined.

Key messages: This review gives an insight into recent findings on TLR10's pro- and anti-inflammatory properties, with the goal of outlining existing results and indicating future research topics on this receptor.

Background: Neutrophils are the first line of defense against pathogens. They are divided into multiple subpopulations during development and kill pathogens through various mechanisms. Neutrophils are considered one of the markers of severe COVID-19.

Summary: In-depth research has revealed that neutrophil subpopulations have multiple complex functions. Different subsets of neutrophils play an important role in the progression of COVID-19.

Key messages: In this review, we provide a detailed overview of the developmental processes of neutrophils at different stages and their recruitment and activation after SARS-CoV-2 infection, aiming to elucidate the changes in neutrophil subpopulations, characteristics, and functions after infection and provide a reference for mechanistic research on neutrophil subpopulations in the context of SARS-CoV-2 infection. In addition, we have also summarized research progress on potential targeted drugs for neutrophil immunotherapy, hoping to provide information that aids the development of therapeutic drugs for the clinical treatment of critically ill COVID-19 patients.