scholarly journals Innate Immunity in Diabetic Wound Healing: Focus on the Mastermind Hidden in Chronic Inflammatory

2021 ◽  
Vol 12 ◽  
Author(s):  
Kang Geng ◽  
Xiumei Ma ◽  
Zongzhe Jiang ◽  
Wei Huang ◽  
Chenlin Gao ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Immune Cell ◽  
Metabolic Stress ◽  
Innate Immune ◽  
Diabetic Wound ◽  
Nonalcoholic Fatty Liver ◽  
Molecular Events ◽  
Immune Pathways ◽  
Molecular Patterns ◽  
Cell Phenotypes

A growing body of evidence suggests that the interaction between immune and metabolic responses is essential for maintaining tissue and organ homeostasis. These interacting disorders contribute to the development of chronic diseases associated with immune-aging such as diabetes, obesity, atherosclerosis, and nonalcoholic fatty liver disease. In Diabetic wound (DW), innate immune cells respond to the Pathogen-associated molecular patterns (PAMAs) and/or Damage-associated molecular patterns (DAMPs), changes from resting to an active phenotype, and play an important role in the triggering and maintenance of inflammation. Furthermore, the abnormal activation of innate immune pathways secondary to immune-aging also plays a key role in DW healing. Here, we review studies of innate immune cellular molecular events that identify metabolic disorders in the local microenvironment of DW and provide a historical perspective. At the same time, we describe some of the recent progress, such as TLR receptor-mediated intracellular signaling pathways that lead to the activation of NF-κB and the production of various pro-inflammatory mediators, NLRP3 inflammatory via pyroptosis, induction of IL-1β and IL-18, cGAS-STING responds to mitochondrial injury and endoplasmic reticulum stress, links sensing of metabolic stress to activation of pro-inflammatory cascades. Besides, JAK-STAT is also involved in DW healing by mediating the action of various innate immune effectors. Finally, we discuss the great potential of targeting these innate immune pathways and reprogramming innate immune cell phenotypes in DW therapy.

scholarly journals The Poxvirus Protein A52R Targets Toll-like Receptor Signaling Complexes to Suppress Host Defense

2003 ◽  
Vol 197 (3) ◽  
pp. 343-351 ◽  
Author(s):  
Mary T. Harte ◽  
Ismar R. Haga ◽  
Geraldine Maloney ◽  
Pearl Gray ◽  
Patrick C. Reading ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Interleukin 1 ◽  
Tumor Necrosis Factor Receptor ◽  
Nuclear Factor Κb ◽  
Innate Immune ◽  
Altered Gene Expression ◽  
Altered Gene ◽  
Molecular Patterns ◽  
Transcription Factor Nuclear Factor ◽  
Necrosis Factor

Toll-like receptors (TLRs) are crucial in the innate immune response to pathogens, in that they recognize and respond to pathogen associated molecular patterns, which leads to activation of intracellular signaling pathways and altered gene expression. Vaccinia virus (VV), the poxvirus used to vaccinate against smallpox, encodes proteins that antagonize important components of host antiviral defense. Here we show that the VV protein A52R blocks the activation of the transcription factor nuclear factor κB (NF-κB) by multiple TLRs, including TLR3, a recently identified receptor for viral RNA. A52R associates with both interleukin 1 receptor–associated kinase 2 (IRAK2) and tumor necrosis factor receptor–associated factor 6 (TRAF6), two key proteins important in TLR signal transduction. Further, A52R could disrupt signaling complexes containing these proteins. A virus deletion mutant lacking the A52R gene was attenuated compared with wild-type and revertant controls in a murine intranasal model of infection. This study reveals a novel mechanism used by VV to suppress the host immunity. We demonstrate viral disabling of TLRs, providing further evidence for an important role for this family of receptors in the antiviral response.

scholarly journals ImmGen report: sexual dimorphism in the immune system transcriptome

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Shani Talia Gal-Oz ◽  
Barbara Maier ◽  
Hideyuki Yoshida ◽  
Kumba Seddu ◽  
Nitzan Elbaz ◽  
...  
Keyword(s):  
Immune System ◽  
Sexual Dimorphism ◽  
Immune Cell ◽  
Cell Types ◽  
Innate Immune ◽  
Male And Female ◽  
Pathogen Invasion ◽  
Immune Pathways ◽  
Genomic Regions ◽  
Mammalian Immune System

Abstract Sexual dimorphism in the mammalian immune system is manifested as more frequent and severe infectious diseases in males and, on the other hand, higher rates of autoimmune disease in females, yet insights underlying those differences are still lacking. Here we characterize sex differences in the immune system by RNA and ATAC sequence profiling of untreated and interferon-induced immune cell types in male and female mice. We detect very few differentially expressed genes between male and female immune cells except in macrophages from three different tissues. Accordingly, very few genomic regions display differences in accessibility between sexes. Transcriptional sexual dimorphism in macrophages is mediated by genes of innate immune pathways, and increases after interferon stimulation. Thus, the stronger immune response of females may be due to more activated innate immune pathways prior to pathogen invasion.

scholarly journals Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses

2009 ◽  
Vol 22 (2) ◽  
pp. 240-273 ◽  
Author(s):  
Trine H. Mogensen
Keyword(s):  
Intracellular Signaling ◽  
Current Knowledge ◽  
Large Family ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Pathogen Recognition ◽  
Inflammatory Signaling ◽  
Subsequent Activation ◽  
Complex Signaling ◽  
Molecular Patterns

SUMMARY The innate immune system constitutes the first line of defense against invading microbial pathogens and relies on a large family of pattern recognition receptors (PRRs), which detect distinct evolutionarily conserved structures on pathogens, termed pathogen-associated molecular patterns (PAMPs). Among the PRRs, the Toll-like receptors have been studied most extensively. Upon PAMP engagement, PRRs trigger intracellular signaling cascades ultimately culminating in the expression of a variety of proinflammatory molecules, which together orchestrate the early host response to infection, and also is a prerequisite for the subsequent activation and shaping of adaptive immunity. In order to avoid immunopathology, this system is tightly regulated by a number of endogenous molecules that limit the magnitude and duration of the inflammatory response. Moreover, pathogenic microbes have developed sophisticated molecular strategies to subvert host defenses by interfering with molecules involved in inflammatory signaling. This review presents current knowledge on pathogen recognition through different families of PRRs and the increasingly complex signaling pathways responsible for activation of an inflammatory and antimicrobial response. Moreover, medical implications are discussed, including the role of PRRs in primary immunodeficiencies and in the pathogenesis of infectious and autoimmune diseases, as well as the possibilities for translation into clinical and therapeutic applications.

scholarly journals The Role of Innate Immune Cells in Nonalcoholic Fatty Liver Disease

2021 ◽  
pp. 1-11
Author(s):  
Marina Nati ◽  
Kyoung-Jin Chung ◽  
Triantafyllos Chavakis
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Immune Cell ◽  
Innate Immune ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Recent Developments ◽  
Macrophage Populations

Nonalcoholic fatty liver disease (NAFLD) is a very common hepatic pathology featuring steatosis and is linked to obesity and related conditions, such as the metabolic syndrome. When hepatic steatosis is accompanied by inflammation, the disorder is defined as nonalcoholic steatohepatitis (NASH), which in turn can progress toward fibrosis development that can ultimately result in cirrhosis. Cells of innate immunity, such as neutrophils or macrophages, are central regulators of NASH-related inflammation. Recent studies utilizing new experimental technologies, such as single-cell RNA sequencing, have revealed substantial heterogeneity within the macrophage populations of the liver, suggesting distinct functions of liver-resident Kupffer cells and recruited monocyte-derived macrophages with regards to regulation of liver inflammation and progression of NASH pathogenesis. Herein, we discuss recent developments concerning the function of innate immune cell subsets in NAFLD and NASH.

scholarly journals Cnidarian Pattern Recognition Receptor Repertoires Reflect Both Phylogeny and Life History Traits

2021 ◽  
Vol 12 ◽  
Author(s):  
Madison A. Emery ◽  
Bradford A. Dimos ◽  
Laura D. Mydlarz
Keyword(s):  
Pattern Recognition ◽  
Innate Immunity ◽  
Life History ◽  
Life History Traits ◽  
Innate Immune ◽  
Immune Pathways ◽  
Immune Pathway ◽  
Molecular Patterns ◽  
Insight Into ◽  
Recognition Receptor

Pattern recognition receptors (PRRs) are evolutionarily ancient and crucial components of innate immunity, recognizing danger-associated molecular patterns (DAMPs) and activating host defenses. Basal non-bilaterian animals such as cnidarians must rely solely on innate immunity to defend themselves from pathogens. By investigating cnidarian PRR repertoires we can gain insight into the evolution of innate immunity in these basal animals. Here we utilize the increasing amount of available genomic resources within Cnidaria to survey the PRR repertoires and downstream immune pathway completeness within 15 cnidarian species spanning two major cnidarian clades, Anthozoa and Medusozoa. Overall, we find that anthozoans possess prototypical PRRs, while medusozoans appear to lack these immune proteins. Additionally, anthozoans consistently had higher numbers of PRRs across all four classes relative to medusozoans, a trend largely driven by expansions in NOD-like receptors and C-type lectins. Symbiotic, sessile, and colonial cnidarians also have expanded PRR repertoires relative to their non-symbiotic, mobile, and solitary counterparts. Interestingly, cnidarians seem to lack key components of mammalian innate immune pathways, though similar to PRR numbers, anthozoans possess more complete immune pathways than medusozoans. Together, our data indicate that anthozoans have greater immune specificity than medusozoans, which we hypothesize to be due to life history traits common within Anthozoa. Overall, this investigation reveals important insights into the evolution of innate immune proteins within these basal animals.

scholarly journals Metabolite Transporters as Regulators of Immunity

Metabolites ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 418
Author(s):  
Hauke J. Weiss ◽  
Stefano Angiari
Keyword(s):  
Intracellular Signaling ◽  
Cell Function ◽  
Immune Cell ◽  
Innate Immune ◽  
Signaling Cascades ◽  
Effector Functions ◽  
Immunological Responses ◽  
The Face ◽  
Specific Receptors

In the past decade, the rise of immunometabolism has fundamentally reshaped the face of immunology. As the functions and properties of many (immuno)metabolites have now been well described, their exchange among cells and their environment have only recently sparked the interest of immunologists. While many metabolites bind specific receptors to induce signaling cascades, some are actively exchanged between cells to communicate, or induce metabolic reprograming. In this review, we give an overview about how active metabolite transport impacts immune cell function and shapes immunological responses. We present some examples of how specific transporters feed into metabolic pathways and initiate intracellular signaling events in immune cells. In particular, we focus on the role of metabolite transporters in the activation and effector functions of T cells and macrophages, as prototype adaptive and innate immune cell populations.

scholarly journals Inhibitory DAMPs in immunogenic cell death and its clinical implications

Cell Stress ◽  
2021 ◽  
Vol 5 (4) ◽  
pp. 52-54
Author(s):  
Kazukuni Hayashi ◽  
Fotis Nikolos ◽  
Keith S. Chan
Keyword(s):  
Cell Death ◽  
Prostaglandin E2 ◽  
Immune Cell ◽  
Innate Immune ◽  
Immunogenic Cell Death ◽  
Clinical Prognosis ◽  
Paracrine Effects ◽  
Cell Mobilization ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Dying (or dead) cells are increasingly recognized to impose significant biological influence within their tissues of residence—exerting paracrine effects through proteins and metabolites that are expressed or secreted during cellular demise. For example, certain molecules function as potent mitogens, promoting the repopulation of neighboring epithelial cells. And other myriad of factors—classified as damage-associated molecular patterns (DAMPs)—function as “find me” (attractant), “eat me” (engulfment), or “danger” (activation) signals for recruiting and activating effector immune cells (e.g., dendritic cells) to initiate inflammation. Since the discovery of immunogenic cell death (ICD), the current dogma posits DAMPs as immunological adjuvants for innate immune cell mobilization and activation, which ultimately leads to the antitumoral cross-priming of CD8+ T cells. However, what is currently unknown is how these immunostimulatory DAMPs are counteracted to avoid immune-overactivation. Our recent work builds on these fundamentals and introduces prostaglandin E2 (PGE2) as an ‘inhibitory’ DAMP—a new variable to the ICD equation. Prostaglandin E2 functions as an immunosuppressive counterpoise of adjuvant DAMPs; and thus, mechanistically precludes ICD. Furthermore, the long-debated immunogenicity of gemcitabine chemotherapy was revealed to be contingent on inhibitory DAMP blockade and not due to its inability to promote DAMP expression (i.e., calreticulin) as previously reported. These findings were intriguing. First, despite the presence of gemcitabine-induced hallmark DAMPs, the inhibitory DAMP (i.e., PGE2) was sufficient to hinder the ICD-induced antitumoral immune response (Fig. 1a). And second, rather than pharmacologically substantiating immunostimulatory DAMPs as conventionally approached, the mitigation of the inhibitory DAMP—tipping the immunostimulatory and inhibitory DAMP balance in favor of immunostimulatory DAMPs—was sufficient to render the cell death immunogenic and converted gemcitabine into an ICD-inducing therapy (Fig. 1b). In this microreview, we extrapolate our findings and implicate the value of inhibitory DAMP(s) in drug discovery, its use for clinical prognosis, and as target(s) for therapeutic intervention.

scholarly journals Toll-like Receptors (TLRs), NOD-like Receptors (NLRs) and RIG-I-like Receptors (RLRs) in Innate Immunity. TLRs, NLRs and RLRs Ligands as Immunotherapeutic Agents for Hematopoietic Diseases

2021 ◽  
Vol 22 (24) ◽  
pp. 13397
Author(s):  
Katarzyna Wicherska-Pawłowska ◽  
Tomasz Wróbel ◽  
Justyna Rybka
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Innate Immune System ◽  
Intracellular Signaling ◽  
Innate Immune ◽  
Toll Like Receptors ◽  
Transmembrane Receptors ◽  
Cancer Immunotherapies ◽  
Molecular Patterns ◽  
Cancer Immunosurveillance

The innate immune system plays a pivotal role in the first line of host defense against infections and is equipped with patterns recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Several classes of PRRS, including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) recognize distinct microbial components and directly activate immune cells. TLRs are transmembrane receptors, while NLRs and RLRs are intracellular molecules. Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of overlapping and unique genes involved in the inflammatory and immune responses. The innate immune system also influences pathways involved in cancer immunosurveillance. Natural and synthetic agonists of TLRs, NLRs, or RLRs can trigger cell death in malignant cells, recruit immune cells, such as DCs, CD8+ T cells, and NK cells, into the tumor microenvironment, and are being explored as promising adjuvants in cancer immunotherapies. In this review, we provide a concise overview of TLRs, NLRs, and RLRs: their structure, functions, signaling pathways, and regulation. We also describe various ligands for these receptors and their possible application in treatment of hematopoietic diseases.

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