Journal of Innate Immunity

INTRODUCTION: Streptococcus pneumoniae is the most common cause of bacterial meningitis and meningoencephalitis in humans. The bacterium produces numerous virulence determinants, among them hydrogen peroxide (H2O2) and pneumolysin (Ply), which contribute to bacterial cytotoxicity. Microglia, the resident phagocytes in the brain, are distinct from other macrophages, and we thus compared their susceptibility to pneumococcal toxicity and their ability to phagocytose pneumococci with those of bone marrow-derived macrophages (BMDM)...

In mice, adenovirus (Ad)-elicited IFN-ab mediates the overproduction of LPS stimulated cytokines such as TNFa and IL-6. We found that Ad infection also mediates the overproduction of IFN-ab itself and enables its production in splenic marginal zone macrophages, which don't produce IFN-ab in response to LPS alone. We show the importance of the scavenger receptor MARCO for Ad uptake and cytokine overproduction in vivo, and the differential contribution of infection and rIFN-b to LPS-induced cytokine response in macrophage subsets...

INTRODUCTION: TNFα-inducible matrix metalloproteinases (MMP) play a critical role in the process of airway remodelling in respiratory inflammatory disease including asthma. The cationic host defence peptide (CHDP) LL-37 is elevated in the lungs during airway inflammation. However, the impact of LL-37 on TNFα-driven processes is not well understood. Here, we examined the effect of LL-37 on TNFα-mediated responses in human bronchial epithelial cells (HBEC). METHODS: We used a Slow Off-rate Modified Aptamer-based proteomics approach to define the HBEC proteome altered in response to TNFα...

INTRODUCTION: Toll-like receptors play crucial roles in sepsis-induced systemic inflammatory response. Septic shock mortality correlates with overexpression of neutrophilic TLR2 and TLR9, while the role of TLR4 overexpression remains a debate. In addition, TLRs are involved in the pathogenesis of viral infections such as COVID-19, where the single-stranded RNA of SARS-CoV-2 is recognized by TLR7 and TLR8, and the spike protein activates TLR4. METHODS: In this study, we conducted a comprehensive analysis of TLRs 1-10 expressions in white blood cells from 71 patients with bacterial and viral infections...

Background Although substantial efforts have been made by researchers to develop drugs, a disappointing reality is that the emergence of drug resistance is an unavoidable reality for the majority of patients. In recent years, emerging evidence suggests a connection between drug resistance and immune dysregulation. Summary As a ubiquitously distributed, versatile innate immune cell, macrophages play essential roles in maintaining tissue homeostasis in steady state. Nevertheless, it is becoming aware that macrophages undermine the action of therapeutic drugs across various disease types...

The brain is considered as an immune-privileged organ, yet innate immune reactions can occur in the central nervous system of vertebrates and invertebrates. Silkworm (Bombyx mori) is an economically important insect and a lepidopteran model species. The diversity of cell types in the silkworm brain, and how these cell subsets produce an immune response to virus infection, remains largely unknown. We used single-nucleus RNA sequencing (snRNA-seq) to identify 19 distinct clusters representing Kenyon cell, glial cell, olfactory projection neuron, optic lobes neuron, hemocyte-like cell, and muscle cell types in the B...

Interleukin-4 (IL-4) is a central regulator of type 2 immunity, crucial for the defense against multicellular parasites like helminths. This study focuses on its roles and cellular sources during Litomosoides sigmodontis infection, a model for human filarial infections. Our research uncovers eosinophils as a major source of IL-4, especially during the early phase of filarial infection. Using dblGATA mice lacking eosinophil and subsequently eosinophil-derived IL-4, we reveal their profound impact on the Th2 response...

INTRODUCTION: Coronavirus disease 2019 (COVID-19) caused by coronavirus-2 (SARS-CoV-2) has emerged as an aggressive viral pandemic. Health care providers confront a challenging task for rapid development of effective strategies to combat this and its long term after effects. Virus entry into host cells involves interaction between receptor-binding domain (RBD) of Spike (S) protein S1 subunit with angiotensin converting enzyme (ACE) present on host cells. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a moonlighting enzyme involved in cellular glycolytic energy metabolism and micronutrient homeostasis...

BACKGROUND: Upon infection, mucosal tissues activate a brisk inflammatory response to clear the pathogen: i.e., resistance to disease. Resistance to disease is orchestrated by tissue-resident macrophages, which undergo profound metabolic reprogramming after sensing the pathogen. These metabolically activated macrophages release many inflammatory factors, which promote their bactericidal function. However, in immunocompetent individuals, pathogens like Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella evade this type of immunity, generating communities that thrive for the long term...

BACKGROUND: Toll-like receptors (TLRs) are one of the first pattern recognition receptors (PRRs) 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, its function and signalling pathway are yet to be determined...

BACKGROUND: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is known as a major receptor for oxidized low-density lipoproteins (oxLDL) and plays a significant role in the genesis of atherosclerosis. Recent research has shown its involvement in cancer, ischemic stroke, and diabetes. LOX-1 is a C-type lectin receptor and involved in the activation of immune cells and inflammatory processes. It may further interact with pathogens, suggesting a role in infections or the host's response...

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...

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INTRODUCTION: The role of vitamin in COVID-19 remains controversial. We investigated the association between endogenous vitamin D and the severity of COVID-19 as well as the mechanisms of action of vitamin D supplementation. METHODS: 25(OH)D3 in serum was associated with disease severity and outcome in 190 COVID-19 patients. In a COVID-19 animal model using intravenous injection of plasma from patients with COVID-19 acute respiratory distress syndrome into C57/BL6 mice, mice were treated with 0...

Hematophagous arthropods can acquire and transmit several pathogens of medical importance. In ticks, the innate immune system is crucial in the outcome between vector-pathogen interaction and overall vector competence. However, the specific immune response(s) elicited by the immune cells known as hemocytes remains largely undefined in Ehrlichia chaffeensis and its competent tick vector, Amblyomma americanum. Here, we show that granulocytes, professional phagocytic cells, are integral in eliciting immune responses against commensal and pathogen infection...

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases. The underlying pathophysiological mechanisms are intricate and involve various factors. Unfortunately, there is currently a lack of available effective treatment options. Toll-like receptors (TLRs) are a group of pattern-recognition receptors that are responsible for activating the innate immune system. Research has demonstrated that TLR4 plays a pivotal role in the progression of MAFLD by facilitating the pathophysiological mechanisms...

INTRODUCTION: C-X-C motif chemokine ligand 1 (CXCL1) is a potent neutrophil chemoattractant that plays a pivotal role in recruiting neutrophils during inflammatory conditions. This study explored the role of CXCL1 in modulating the gut microbiota, influencing neutrophil infiltration, and contributing to the development of colitis. METHODS: We employed quantitative PCR to assess CXCL1 expression in colon samples. A mouse model of DSS-induced colitis was utilized to explore the progression of colitis in wild-type (WT) and CXCL1-deficient (CXCL1-/-) mice...

INTRODUCTION: C3 is central for all complement activation pathways, thus an attractive therapeutic target. Many C3-targeted agents are under extensive development with one already approved for clinical use. However, most, if not all, C3 inhibitors are human or non-human primate C3-specific, making evaluating their efficacies in vivo before a clinical trial extremely difficult and costly. METHODS: We first studied the compatibility of human C3 in the rat complement system, then developed a C3 humanized rat using the CRISPR/Cas9 technology...

Staphylococcus aureus (S. aureus) is a common cause of hospital- and community-acquired infections that can result in various clinical manifestations ranging from mild to severe disease. The bacterium utilizes different combinations of virulence factors and biofilm formation to establish a successful infection, and the emergence of methicillin- and vancomycin-resistant strains introduces additional challenges for infection management and treatment. Metabolic programming of immune cells regulates the balance of energy requirements for activation and dictates pro- vs...

Background Innate immune cells play a crucial role in responding to microbial infections, but their improper activation can also drive inflammatory disease. For this reason, their activation state is governed by a multitude of factors, including the metabolic state of the cell and, more specifically, the individual metabolites which accumulate intra- and extra-cellularly. This relationship is bidirectional, as innate immune cell activation by pathogen-associated molecular patterns (PAMPs) causes critical changes in cellular metabolism...