lncRNAs Regulate Innate Immune Responses and Their Roles in Macrophage Polarization

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

The innate immune system

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0038 ◽

2020 ◽

pp. 307-314

Author(s):

Paul Bowness

Keyword(s):

Immune System ◽

Immune Responses ◽

Innate Immune System ◽

Cell Types ◽

Innate Immune ◽

Microbial Pathogens ◽

Innate Immune Responses ◽

Adaptive Immune ◽

System P ◽

Different Cell Types

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

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

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

Environmental Science Nano ◽

10.1039/c8en00002f ◽

2018 ◽

Vol 5 (4) ◽

pp. 904-916 ◽

Cited By ~ 20

Author(s):

Nadja R. Brun ◽

Bjørn E. V. Koch ◽

Mónica Varela ◽

Willie J. G. M. Peijnenburg ◽

Herman P. Spaink ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Innate Immune System ◽

Innate Immune ◽

Zebrafish Embryos ◽

Innate Immune Responses

Metal and plastic nanoparticles elicit innate immune responses in the skin and intestine of zebrafish embryos potentially serving as key event for AOPs.

Download Full-text

Innate Pathways of Immune Activation in Transplantation

Journal of Transplantation ◽

10.1155/2010/826240 ◽

2010 ◽

Vol 2010 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Todd V. Brennan ◽

Keri E. Lunsford ◽

Paul C. Kuo

Keyword(s):

Immune System ◽

Innate Immune System ◽

Critical Role ◽

Adaptive Immune System ◽

Innate Immune ◽

Microbial Pathogens ◽

Immune Recognition ◽

First Line ◽

Adaptive Immune

Studies of the immune mechanisms of allograft rejection have predominantly focused on the adaptive immune system that includes T cells and B cells. Recent investigations into the innate immune system, which recognizes foreign antigens through more evolutionarily primitive pathways, have demonstrated a critical role of the innate immune system in the regulation of the adaptive immune system. Innate immunity has been extensively studied in its role as the host's first-line defense against microbial pathogens; however, it is becoming increasingly recognized for its ability to also recognize host-derived molecules that result from tissue damage. The capacity of endogenous damage signals acting through the innate immune system to lower immune thresholds and promote immune recognition and rejection of transplant grafts is only beginning to be appreciated. An improved understanding of these pathways may reveal novel therapeutic targets to decrease graft alloreactivity and increase graft longevity.

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

Host Innate Immune Responses to Microbial Pathogens

Current Vascular Pharmacology ◽

10.2174/157016113805290218 ◽

2013 ◽

Vol 11 (2) ◽

pp. 123-132

Author(s):

Julie Delaloye ◽

Thierry Calandra

Keyword(s):

Immune Responses ◽

Innate Immune ◽

Microbial Pathogens ◽

Innate Immune Responses

Download Full-text

Emerging Roles of Protein Deamidation in Innate Immune Signaling

Journal of Virology ◽

10.1128/jvi.01980-15 ◽

2016 ◽

Vol 90 (9) ◽

pp. 4262-4268 ◽

Cited By ~ 20

Author(s):

Jun Zhao ◽

Junhua Li ◽

Simin Xu ◽

Pinghui Feng

Keyword(s):

Immune Responses ◽

Innate Immune ◽

Microbial Pathogens ◽

Biological Processes ◽

Innate Immune Responses ◽

Immune Signaling ◽

Host Immune Responses ◽

Innate Immune Signaling ◽

Enzyme Deficient ◽

Signaling Components

Protein deamidation has been considered a nonenzymatic process associated with protein functional decay or “aging.” Recent studies implicate protein deamidation in regulating signal transduction in fundamental biological processes, such as innate immune responses. Work investigating gammaherpesviruses and bacterial pathogens indicates that microbial pathogens deploy deamidases or enzyme-deficient homologues (pseudoenzymes) to induce deamidation of key signaling components and evade host immune responses. Here, we review studies on protein deamidation in innate immune signaling and present several imminent questions concerning the roles of protein deamidation in infection and immunity.

Download Full-text

Beneficial and Harmful Interactions of Antibiotics with Microbial Pathogens and the Host Innate Immune System

Pharmaceuticals ◽

10.3390/ph3051694 ◽

2010 ◽

Vol 3 (5) ◽

pp. 1694-1710 ◽

Cited By ~ 13

Author(s):

Ronald Anderson ◽

Gregory Tintinger ◽

Riana Cockeran ◽

Moliehi Potjo ◽

Charles Feldman

Keyword(s):

Immune System ◽

Innate Immune System ◽

Innate Immune ◽

Microbial Pathogens

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

Ironing Out the Details: How Iron Orchestrates Macrophage Polarization

Frontiers in Immunology ◽

10.3389/fimmu.2021.669566 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yaoyao Xia ◽

Yikun Li ◽

Xiaoyan Wu ◽

Qingzhuo Zhang ◽

Siyuan Chen ◽

...

Keyword(s):

Adjuvant Therapy ◽

Immune Responses ◽

Epigenetic Regulation ◽

Crucial Role ◽

Liver Diseases ◽

Iron Supplementation ◽

Macrophage Polarization ◽

Innate Immune ◽

Innate Immune Responses

Iron fine-tunes innate immune responses, including macrophage inflammation. In this review, we summarize the current understanding about the iron in dictating macrophage polarization. Mechanistically, iron orchestrates macrophage polarization through several aspects, including cellular signaling, cellular metabolism, and epigenetic regulation. Therefore, iron modulates the development and progression of multiple macrophage-associated diseases, such as cancer, atherosclerosis, and liver diseases. Collectively, this review highlights the crucial role of iron for macrophage polarization, and indicates the potential application of iron supplementation as an adjuvant therapy in different inflammatory disorders relative to the balance of macrophage polarization.

Download Full-text