Nanoparticles induce dermal and intestinal innate immune system responses in zebrafish embryos

The innate immune system comprises evolutionarily ancient mechanisms that mediate first-line responses against microbial pathogens, and are also important in priming and execution of adaptive immune responses, and in defence against tumours. These responses, which recognize microbial non-self, damaged self, and absent self, are characterized by rapidity of action and they involve various different cell types, cell-associated receptors, and soluble factors. Previously thought to lack plasticity or memory, certain innate immune responses have recently been shown to be capable of ‘learning’ or ‘training’. Most cells of the innate immune system are derived from the myeloid precursors in the bone marrow. These include monocytes and their derivatives—macrophages and dendritic cells, blood granulocytes (neutrophils, basophils, and eosinophils), and tissue mast cells.

Download Full-text

lncRNAs Regulate Innate Immune Responses and Their Roles in Macrophage Polarization

Mediators of Inflammation ◽

10.1155/2018/8050956 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 13

Author(s):

Zhen Wang ◽

Ying Zheng

Keyword(s):

Immune System ◽

Immune Responses ◽

Innate Immune System ◽

Macrophage Polarization ◽

Noncoding Rnas ◽

Innate Immune ◽

Microbial Pathogens ◽

Innate Immune Responses ◽

First Line ◽

New Class

The innate immune system is the first line of defense against microbial pathogens. The activated innate immune system plays important roles in eliciting antimicrobial defenses. Despite the benefits of innate immune responses, excessive inflammation will cause host damage. Thus, tight regulation of these processes is required for the maintenance of immune homeostasis. Recently, a new class of long noncoding RNAs (lncRNAs) has emerged as important regulators in many physiological and pathological processes. Dysregulated lncRNAs have been found to be associated with excessive or uncontrolled inflammation. In this brief review, we summarize the roles of functional lncRNAs in regulating innate immune responses. We also discuss the roles of lncRNAs in macrophage polarization, an important molecular event in the innate immune responses.

Download Full-text

Retrovirus-derived acquired genes, RTL5 and RTL6, are novel constituents of the innate immune system in the eutherian brain.

10.1101/2021.12.29.474483 ◽

2021 ◽

Author(s):

Masahito Irie ◽

Johbu Itoh ◽

Ayumi Matsuzawa ◽

Masahito Ikawa ◽

Toru Suzuki ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Innate Immune System ◽

Basic Protein ◽

Innate Immune ◽

Hazardous Substances ◽

Innate Immune Responses ◽

Front Line ◽

Cpg Dna ◽

Mature Brain

Retrotransposon Gag-like 5 (RTL5, also known as sushi-ichi-related retrotransposon homolog 8 (SIRH8)) and RTL6 (aka SIRH3) are eutherian-specific genes presumably derived from a retrovirus and phylogenetically related to each other. RTL5 encodes a strongly acidic protein while RTL6 encodes an extremely basic protein, and the former is well conserved and the latter extremely well conserved among the eutherians, indicating their unique and critically important roles as acquired genes. Here we report that RTL5 and RTL6 are microglial genes playing roles in the front line of brain innate immune responses against distinct pathogens. Venus and mCherry knock-in mice exhibited expression of RTL5-mCherry and RTL6-Venus fusion proteins in microglia and as extracellular granules in the central nervus system (CNS), and displayed a rapid response to pathogens such as lipopolysaccharide (LPS), double-stranded (ds) RNA analog and non-methylated CpG DNA. These proteins trapped pathogens in microglia in a variety of RTL-pathogen complexes depending on the pathogens. These results demonstrate that RTL5 and RTL6 exert functional effects against different hazardous substances cooperatively and/or independently to protect the developing and/or mature brain. This provides the first evidence that retrovirus-derived genes play a role in the innate immune system of the eutherian brain.

Download Full-text

Commensal and Opportunistic Bacteria Present in the Microbiota in Atlantic Cod (Gadus morhua) Larvae Differentially Alter the Hosts’ Innate Immune Responses

Microorganisms ◽

10.3390/microorganisms10010024 ◽

2021 ◽

Vol 10 (1) ◽

pp. 24

Author(s):

Ragnhild Inderberg Vestrum ◽

Torunn Forberg ◽

Birgit Luef ◽

Ingrid Bakke ◽

Per Winge ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Atlantic Cod ◽

Innate Immune ◽

Rrna Gene ◽

Innate Immune Responses ◽

Transcriptional Responses ◽

Gut Morphology ◽

Germ Free ◽

Opportunistic Bacteria

The roles of host-associated bacteria have gained attention lately, and we now recognise that the microbiota is essential in processes such as digestion, development of the immune system and gut function. In this study, Atlantic cod larvae were reared under germ-free, gnotobiotic and conventional conditions. Water and fish microbiota were characterised by 16S rRNA gene analyses. The cod larvae’s transcriptional responses to the different microbial conditions were analysed by a custom Agilent 44 k oligo microarray. Gut development was assessed by transmission electron microscopy (TEM). Water and fish microbiota differed significantly in the conventional treatment and were dominated by different fast-growing bacteria. Our study indicates that components of the innate immune system of cod larvae are downregulated by the presence of non-pathogenic bacteria, and thus may be turned on by default in the early larval stages. We see indications of decreased nutrient uptake in the absence of bacteria. The bacteria also influence the gut morphology, reflected in shorter microvilli with higher density in the conventional larvae than in the germ-free larvae. The fact that the microbiota alters innate immune responses and gut morphology demonstrates its important role in marine larval development.

Download Full-text

Mitochondria surveillance systems trigger innate immune responses to bacterial pathogens via AMPK pathway in C. elegans

10.1101/2020.09.17.301036 ◽

2020 ◽

Author(s):

Shouyong Ju ◽

Hanqiao Chen ◽

Shaoying Wang ◽

Jian Lin ◽

Raffi V Aroian ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Innate Immune ◽

Surveillance Systems ◽

Innate Immune Responses ◽

Energy Status ◽

Microbial Infection ◽

C Elegans ◽

Host Interaction ◽

Intracellular Energy

AbstractPathogen recognition and triggering pattern of host innate immune system is critical to understanding pathogen-host interaction. It is generally accepted that the microbial infection can be recognized by host via pattern-triggered immunity (PTI) or effector-triggered immunity (ETI) responses. Recently, non-PRR-mediated cellular surveillance systems have been reported as an important supplement strategy to PTI and ETI responses. However, the mechanism of how surveillance systems sense pathogens and trigger innate immune responses is largely unknown. In the present study, using Bacillus thuringiensis-Caenorhabditis elegans as a model, we found a new approach for surveillance systems to sense the pathogens through no-PPRs patterns. We reported C. elegans can monitor intracellular energy status through the mitochondrial surveillance system to triggered innate immune responses against pathogenic attack via AMP-activated protein kinase (AMPK). Consider that the mitochondria surveillance systems and AMPK are conserved components from worms to mammals, our study suggests that disrupting mitochondrial homeostasis to activate the immune system through AMPK-dependent pathways may widely existing in animals.

Download Full-text

The neuropeptide receptor NMUR-1 regulates the specificity of C. elegans innate immunity against pathogen infection

10.1101/2021.05.06.442992 ◽

2021 ◽

Author(s):

Phillip Wibisono ◽

Shawndra Wibisono ◽

Jan Watteyne ◽

Chia-Hui Chen ◽

Durai Sellegounder ◽

...

Keyword(s):

Innate Immunity ◽

Immune System ◽

Immune Responses ◽

Adaptive Immune System ◽

Innate Immune ◽

Innate Immune Responses ◽

Immune Genes ◽

C Elegans ◽

Adaptive Immune ◽

Functional Assays

A key question in current immunology is how the innate immune system generates high levels of specificity. Like most invertebrates, Caenorhabditis elegans does not have an adaptive immune system and relies solely on innate immunity to defend itself against pathogen attacks, yet it can still differentiate different pathogens and launch distinct innate immune responses. Here, we have found that functional loss of NMUR-1, a neuronal GPCR homologous to mammalian receptors for the neuropeptide neuromedin U, has diverse effects on C. elegans survival against various bacterial pathogens. Transcriptomic analyses and functional assays revealed that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors, which, in turn, controls the expression of distinct immune genes in response to different pathogens. Our study has uncovered a molecular basis for the specificity of C. elegans innate immunity that could provide mechanistic insights into understanding the specificity of vertebrate innate immunity.

Download Full-text

Innate immunity and the pneumococcus

Microbiology ◽

10.1099/mic.0.28551-0 ◽

2006 ◽

Vol 152 (2) ◽

pp. 285-293 ◽

Cited By ~ 52

Author(s):

Gavin K. Paterson ◽

Tim J. Mitchell

Keyword(s):

Innate Immunity ◽

Immune System ◽

Streptococcus Pneumoniae ◽

Immune Responses ◽

Innate Immune System ◽

Innate Immune ◽

First Line ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Made In

The innate immune system provides a non-specific first line of defence against microbes and is crucial both in the development and effector stages of subsequent adaptive immune responses. Consistent with its importance, study of the innate immune system is a broad and fast-moving field. Here we provide an overview of the recent key advances made in this area with relation to the important pathogen Streptococcus pneumoniae (the pneumococcus).

Download Full-text

Phenoloxidase activity and haemolymph cytology in honeybees challenged with a virus suspension (deformed wings virus DWV) or phosphate buffered suspension (PBS)

Ciência Rural ◽

10.1590/0103-8478cr20180726 ◽

2019 ◽

Vol 49 (2) ◽

Cited By ~ 3

Author(s):

Francesca Millanta ◽

Simona Sagona ◽

Maurizio Mazzei ◽

Mario Forzan ◽

Alessandro Poli ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Immune Responses ◽

Innate Immune System ◽

Innate Immune ◽

Additional Stress ◽

Varroa Mite ◽

Virus Suspension ◽

Phenoloxidase Activity ◽

Cell Immunity

ABSTRACT: The innate immune system of honeybees mainly consists in antimicrobial peptides, cellular immunity and melanisation. In order to investigate the immune response of honeybees to immune stressors, three stress degrees were tested. Newly emerged bees naturally DWV-infected were collected from a Varroa mite-free apiary and divided into three experimental groups: naturally DWV infected bees, PBS injected bees, and artificially DWV super infected bees. Phenoloxidase activity and haemolymph cellular subtype count were investigated. Phenoloxidase activity was highest (P<0.05) in DWV-superinfected bees, and the haemocyte population differed within the three observed groups. Although, immune responses following DWV infection have still not been completely clarified, this investigation sheds light on the relation between cell immunity and the phenoloxidase activity of DWV-naturally infected honeybees exposed to additional stress such as injury and viral superinfection.

Download Full-text

Tweaking Innate Immunity: The Promise of Innate Immunologicals as Anti-Infectives

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2006/195957 ◽

2006 ◽

Vol 17 (5) ◽

pp. 307-314 ◽

Cited By ~ 8

Author(s):

Kenneth L Rosenthal

Keyword(s):

Innate Immunity ◽

Immune System ◽

Immune Responses ◽

Innate Immune System ◽

Immune Defense ◽

Innate Immune ◽

Parasitic Infections ◽

Type I ◽

Adaptive Immune Responses ◽

Adaptive Immune

New and exciting insights into the importance of the innate immune system are revolutionizing our understanding of immune defense against infections, pathogenesis, and the treatment and prevention of infectious diseases. The innate immune system uses multiple families of germline-encoded pattern recognition receptors (PRRs) to detect infection and trigger a variety of antimicrobial defense mechanisms. PRRs are evolutionarily highly conserved and serve to detect infection by recognizing pathogen-associated molecular patterns that are unique to microorganisms and essential for their survival. Toll-like receptors (TLRs) are transmembrane signalling receptors that activate gene expression programs that result in the production of proinflammatory cytokines and chemokines, type I interferons and antimicrobial factors. Furthermore, TLR activation facilitates and guides activation of adaptive immune responses through the activation of dendritic cells. TLRs are localized on the cell surface and in endosomal/lysosomal compartments, where they detect bacterial and viral infections. In contrast, nucleotide-binding oligomerization domain proteins and RNA helicases are located in the cell cytoplasm, where they serve as intracellular PRRs to detect cytoplasmic infections, particularly viruses. Due to their ability to enhance innate immune responses, novel strategies to use ligands, synthetic agonists or antagonists of PRRs (also known as 'innate immunologicals') can be used as stand-alone agents to provide immediate protection or treatment against bacterial, viral or parasitic infections. Furthermore, the newly appreciated importance of innate immunity in initiating and shaping adaptive immune responses is contributing to our understanding of vaccine adjuvants and promises to lead to improved next-generation vaccines.

Download Full-text

Structural aspects of molecular recognition in the immune system. Part II: Pattern recognition receptors (IUPAC Technical Report)

Pure and Applied Chemistry ◽

10.1515/pac-2013-1026 ◽

2014 ◽

Vol 86 (10) ◽

pp. 1483-1538 ◽

Cited By ~ 4

Author(s):

John A. Robinson ◽

Kerstin Moehle

Keyword(s):

Pattern Recognition ◽

Immune System ◽

Immune Responses ◽

Signaling Pathways ◽

Innate Immune System ◽

Pattern Recognition Receptors ◽

Innate Immune ◽

Helicase Domain ◽

Downstream Signaling ◽

Adaptive Immune

Abstract The vertebrate immune system uses pattern recognition receptors (PRRs) to detect a large variety of molecular signatures (pathogen-associated molecular patterns, PAMPs) from a broad range of different invading pathogens. The PAMPs range in size from relatively small molecules, to others of intermediate size such as bacterial lipopolysaccharide, lipopeptides, and oligosaccharides, to macromolecules such as viral DNA, RNA, and pathogen-derived proteins such as flagellin. Underlying this functional diversity of PRRs is a surprisingly small number of structurally distinct protein folds that include leucine-rich repeats in Toll-like receptors (TLRs) and NOD-like receptors (NLRs), the DExH box helicase domain in RIG-like receptors (RLRs), and C-type lectin domains (CTLDs) in the C-type lectins. Following PAMP recognition by the PRRs, downstream signaling pathways activate the innate immune system to respond to invading pathogenic organisms. The resulting stimulatory response is also vital for a balanced adaptive immune response to the pathogen, mediated by circulating antibodies and/or cytotoxic T cells. However, an aberrant stimulation of the innate immune system can also lead to excessive inflammatory and toxic stress responses. Exciting opportunities are now arising for the design of small synthetic molecules that bind to PRRs and influence downstream signaling pathways. Such molecules can be useful tools to modulate immune responses, for example, as adjuvants to stimulate adaptive immune responses to a vaccine, or as therapeutic agents to dampen aberrant immune responses, such as inflammation. The design of agonists or antagonists of PRRs can now benefit from a surge in knowledge of the 3D structures of PRRs, many in complexes with their natural ligands. This review article describes recent progress in structural studies of PRRs (TLRs, NLRs, CTLs, and RLRs), which is required for an understanding of how they specifically recognize structurally diverse “foreign” PAMPs amongst a background of other “self” molecules, sometimes closely related in structure, that are present in the human body.

Download Full-text