scholarly journals Dynamic roles of inflammasomes in inflammatory tumor microenvironment

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Jeong-Hoon Jang ◽  
Do-Hee Kim ◽  
Young-Joon Surh
Keyword(s):  
Tumor Microenvironment ◽  
Immune Responses ◽  
Vital Role ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
First Line ◽  
Master Regulators ◽  
Downstream Effector ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

AbstractThe inflammatory tumor microenvironment has been known to be closely connected to all stages of cancer development, including initiation, promotion, and progression. Systemic inflammation in the tumor microenvironment is increasingly being recognized as an important prognostic marker in cancer patients. Inflammasomes are master regulators in the first line of host defense for the initiation of innate immune responses. Inflammasomes sense pathogen-associated molecular patterns and damage-associated molecular patterns, following recruitment of immune cells into infection sites. Therefore, dysregulated expression/activation of inflammasomes is implicated in pathogenesis of diverse inflammatory disorders. Recent studies have demonstrated that inflammasomes play a vital role in regulating the development and progression of cancer. This review focuses on fate-determining roles of the inflammasomes and the principal downstream effector cytokine, IL-1β, in the tumor microenvironment.

scholarly journals Innate immunology in COVID-19—a living review. Part II: dysregulated inflammation drives immunopathology

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Patrícia R S Rodrigues ◽  
Aljawharah Alrubayyi ◽  
Ellie Pring ◽  
Valentina M T Bart ◽  
Ruth Jones ◽  
...  
Keyword(s):  
Immune Responses ◽  
Current Knowledge ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Responses ◽  
Innate Immunology ◽  
Viral Pathogen ◽  
Health Crisis ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Abstract The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health crisis and will likely continue to impact public health for years. As the effectiveness of the innate immune response is crucial to patient outcome, huge efforts have been made to understand how dysregulated immune responses may contribute to disease progression. Here we have reviewed current knowledge of cellular innate immune responses to SARS-CoV-2 infection, highlighting areas for further investigation and suggesting potential strategies for intervention. We conclude that in severe COVID-19 initial innate responses, primarily type I interferon, are suppressed or sabotaged which results in an early interleukin (IL)-6, IL-10 and IL-1β-enhanced hyperinflammation. This inflammatory environment is driven by aberrant function of innate immune cells: monocytes, macrophages and natural killer cells dispersing viral pathogen-associated molecular patterns and damage-associated molecular patterns into tissues. This results in primarily neutrophil-driven pathology including fibrosis that causes acute respiratory distress syndrome. Activated leukocytes and neutrophil extracellular traps also promote immunothrombotic clots that embed into the lungs and kidneys of severe COVID-19 patients, are worsened by immobility in the intensive care unit and are perhaps responsible for the high mortality. Therefore, treatments that target inflammation and coagulation are promising strategies for reducing mortality in COVID-19.

scholarly journals The Role of Toll-Like Receptor Signaling in the Progression of Heart Failure

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Lili Yu ◽  
Zhiwei Feng
Keyword(s):  
Heart Failure ◽  
Immune Responses ◽  
Target Therapy ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Medical Systems ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Tlr Signaling Pathway

Medical systems worldwide are being faced with a growing need to understand mechanisms behind the pathogenesis of heart failure (HF) that is considered as a leading cause of morbidity and mortality around the world. Elevated levels of inflammatory mediators have been identified in patients with HF, which are primarily manifestations of innate immune responses mediated by pattern recognition receptors (PRRs). Toll-like receptors (TLRs), which belong to PRRs, are subjected to the release of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) to generate innate immune responses. More and more emerging data indicate that TLR signaling pathway molecules are involved in the progression of HF. Herein, we present new data with regard to the activation of TLRs in the failing heart, focusing on TLR2, TLR3, TLR4, and TLR9, and suggest the potential use of TLRs in target therapy.

scholarly journals The First Line of Defense: Receptor-like Protein Kinase-Mediated Stomatal Immunity

2021 ◽  
Vol 23 (1) ◽  
pp. 343
Author(s):  
Zhe Wang ◽  
Xiaoping Gou
Keyword(s):  
Immune Responses ◽  
Water Exchange ◽  
Guard Cells ◽  
Innate Immune ◽  
Research Progress ◽  
Future Research ◽  
Bacterial Invasion ◽  
Innate Immune Responses ◽  
First Line ◽  
Molecular Patterns

Stomata regulate gas and water exchange between the plant and external atmosphere, which are vital for photosynthesis and transpiration. Stomata are also the natural entrance for pathogens invading into the apoplast. Therefore, stomata play an important role in plants against pathogens. The pattern recognition receptors (PRRs) locate in guard cells to perceive pathogen/microbe-associated molecular patterns (PAMPs) and trigger a series of plant innate immune responses, including rapid closure of stomata to limit bacterial invasion, which is termed stomatal immunity. Many PRRs involved in stomatal immunity are plasma membrane-located receptor-like protein kinases (RLKs). This review focuses on the current research progress of RLK-mediated signaling pathways involved in stomatal immunity, and discusses questions that need to be addressed in future research.

scholarly journals The Role of Peptide Signals Hidden in the Structure of Functional Proteins in Plant Immune Responses

2019 ◽  
Vol 20 (18) ◽  
pp. 4343 ◽  
Author(s):  
Irina Lyapina ◽  
Anna Filippova ◽  
Igor Fesenko
Keyword(s):  
Immune Responses ◽  
Defense Responses ◽  
Innate Immune ◽  
Functional Protein ◽  
Diverse Range ◽  
Peptide Signals ◽  
Plant Pathogen Interactions ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Plants have evolved a sophisticated innate immune system to cope with a diverse range of phytopathogens and insect herbivores. Plasma-membrane-localized pattern recognition receptors (PRRs), such as receptor-like kinases (RLK), recognize special signals, pathogen- or damage-associated molecular patterns (PAMPs or DAMPs), and trigger immune responses. A growing body of evidence shows that many peptides hidden in both plant and pathogen functional protein sequences belong to the group of such immune signals. However, the origin, evolution, and release mechanisms of peptide sequences from functional and nonfunctional protein precursors, known as cryptic peptides, are largely unknown. Various special proteases, such as metacaspase or subtilisin-like proteases, are involved in the release of such peptides upon activation during defense responses. In this review, we discuss the roles of cryptic peptide sequences hidden in the structure of functional proteins in plant defense and plant-pathogen interactions.

scholarly journals Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nham Tran ◽  
Alison Ricafrente ◽  
Joyce To ◽  
Maria Lund ◽  
Tania M. Marques ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cell Function ◽  
Fasciola Hepatica ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Defence Mechanisms ◽  
First Line ◽  
M1 Macrophages ◽  
Successful Infection ◽  
Inflammatory Immune Response

AbstractFasciola hepatica, a global worm parasite of humans and their livestock, regulates host innate immune responses within hours of infection. Host macrophages, essential to the first-line defence mechanisms, are quickly restricted in their ability to initiate a classic protective pro-inflammatory immune response. We found that macrophages from infected animals are enriched with parasite-derived micro(mi)RNAs. The most abundant of these miRNAs, fhe-miR-125b, is released by the parasite via exosomes and is homologous to a mammalian miRNA, hsa-miR-125b, that is known to regulate the activation of pro-inflammatory M1 macrophages. We show that the parasite fhe-miR-125b loads onto the mammalian Argonaut protein (Ago-2) within macrophages during infection and, therefore, propose that it mimics host miR-125b to negatively regulate the production of inflammatory cytokines. The hijacking of the miRNA machinery controlling innate cell function could be a fundamental mechanism by which worm parasites disarm the early immune responses of their host to ensure successful infection.

scholarly journals Patho-immunological mechanisms of vitiligo: an integration of the immunogenetic milieu, with innate and adaptive immunities, as triggered by environmental stress factors

2021 ◽  
Author(s):  
Safa Faraj ◽  
E H Kemp ◽  
DAVID GAWKRODGER
Keyword(s):  
Immune Responses ◽  
Pigment Cell ◽  
Chemical Exposure ◽  
Innate Immune ◽  
Stress Factors ◽  
Pigment Cells ◽  
Innate Immune Responses ◽  
Autoreactive T Cell ◽  
Immunological Mechanisms ◽  
Molecular Patterns

Epidermal melanocyte loss in vitiligo, triggered by stresses ranging from trauma to emo-tional stress, chemical exposure or metabolite imbalance, to the unknown, can stimulate oxidative stress in pigment cells which secrete damage-associated molecular patterns that then initiate innate immune responses. Antigen presentation to melanocytes leads to stim-ulation of autoreactive T cell responses, with further targeting of pigment cell. Studies show a pathogenic basis for cellular stress, innate immune responses and adaptive immun-ity in vitiligo. Improved understanding of the aetiological mechanisms in vitiligo has already resulted in successful use of the Jak-1 inhibitors in vitiligo. In this review we outline the cur-rent understanding of the pathological mechanisms in vitiligo, and locate loci to which therapeutic attack might be directed.

PRRs in pathogen recognition

2006 ◽  
Vol 1 (3) ◽  
pp. 299-313 ◽  
Author(s):  
Satoshi Uematsu ◽  
Shizuo Akira
Keyword(s):  
Pattern Recognition ◽  
Immune Responses ◽  
Pattern Recognition Receptors ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Pathogen Recognition ◽  
First Line ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Wide Range

AbstractThe innate immune system provides the first line of host defense against invading microorganisms before the development of adaptive immune responses. Innate immune responses are initiated by germline-encoded pattern recognition receptors (PRRs), which recognize specific structures of microorganisms. Toll-like receptors (TLRs) are pattern-recognition receptors that sense a wide range of microorganisms, including bacteria, fungi, protozoa and viruses. TLRs exist either on the cell surface or in the lysosome/endosome compartment and induce innate immune responses. Recently, cytoplasmic PRRs have been identified which detect pathogens that have invaded the cytosol. This review focuses on the pathogen recognition of PRRs in innate immunity.

scholarly journals PKA/KIN-1 mediates innate immune responses to bacterial pathogens in Caenorhabditis elegans

2017 ◽  
Vol 23 (8) ◽  
pp. 656-666 ◽  
Author(s):  
Yi Xiao ◽  
Fang Liu ◽  
Pei-ji Zhao ◽  
Cheng-Gang Zou ◽  
Ke-Qin Zhang
Keyword(s):  
Innate Immunity ◽  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Immune Responses ◽  
Innate Immune ◽  
Autophagic Flux ◽  
Innate Immune Responses ◽  
C Elegans ◽  
Downstream Effector ◽  
Model Animal

The genetically tractable organism Caenorhabditis elegans is a powerful model animal for the study of host innate immunity. Although the intestine and the epidermis of C. elegans that is in contact with pathogens are likely to function as sites for the immune function, recent studies indicate that the nervous system could control innate immunity in C. elegans. In this report, we demonstrated that protein kinase A (PKA)/KIN-1 in the neurons contributes to resistance against Salmonella enterica infection in C. elegans. Microarray analysis revealed that PKA/KIN-1 regulates the expression of a set of antimicrobial effectors in the non-neuron tissues, which are required for innate immune responses to S. enterica. Furthermore, PKA/KIN-1 regulated the expression of lysosomal genes during S. enterica infection. Our results suggest that the lysosomal signaling molecules are involved in autophagy by controlling autophagic flux, rather than formation of autophagosomes. As autophagy is crucial for host defense against S. enterica infection in a metazoan, the lysosomal pathway also acts as a downstream effector of the PKA/KIN-1 signaling for innate immunity. Our data indicate that the PKA pathway contributes to innate immunity in C. elegans by signaling from the nervous system to periphery tissues to protect the host against pathogens.

scholarly journals lncRNAs Regulate Innate Immune Responses and Their Roles in Macrophage Polarization

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
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.

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