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Allergology International : Official... Apr 2021Group 2 innate lymphoid cells (ILC2s) reside in peripheral tissues such as the lungs, skin, nasal cavity, and gut and provoke innate type 2 immunity against allergen... (Review)
Review
Group 2 innate lymphoid cells (ILC2s) reside in peripheral tissues such as the lungs, skin, nasal cavity, and gut and provoke innate type 2 immunity against allergen exposure, parasitic worm infection, and respiratory virus infection by producing T2 cytokines. Recent advances in understanding ILC2 biology revealed that ILC2s can be trained by IL-33 or allergic inflammation, are long-lived, and mount memory-like type 2 immune responses to any other allergens afterwards. In contrast, IL-33, together with retinoic acid, induces IL-10-producing immunosuppressive ILC2s. In this review, we discuss how the allergic cytokine milieu and other immune cells direct the generation of trained ILC2s with immunostimulatory or immunosuppressive recall capability in allergic diseases and infections associated with type 2 immunity. The molecular mechanisms of trained immunity by ILCs and the physiological relevance of trained ILC2s are also discussed.
Topics: Alarmins; Animals; Cell Communication; Humans; Hypersensitivity; Immunity, Innate; Inflammation Mediators; Interleukin-10; Interleukin-33; Lipids; Lymphocytes; Neurons; Virus Diseases
PubMed: 33328130
DOI: 10.1016/j.alit.2020.11.007 -
Journal of Immunology Research 2021Toll-like receptors (TLRs) are pivotal biomolecules in the immune system. Today, we are all aware of the importance of TLRs in bridging innate and adaptive immune system... (Review)
Review
BACKGROUND/AIM
Toll-like receptors (TLRs) are pivotal biomolecules in the immune system. Today, we are all aware of the importance of TLRs in bridging innate and adaptive immune system to each other. The TLRs are activated through binding to damage/danger-associated molecular patterns (DAMPs), microbial/microbe-associated molecular patterns (MAMPs), pathogen-associated molecular patterns (PAMPs), and xenobiotic-associated molecular patterns (XAMPs). The immunogenetic molecules of TLRs have their own functions, structures, coreceptors, and ligands which make them unique. These properties of TLRs give us an opportunity to find out how we can employ this knowledge for ligand-drug discovery strategies to control TLRs functions and contribution, signaling pathways, and indirect activities. Hence, the authors of this paper have a deep observation on the molecular and structural biology of human TLRs (hTLRs).
METHODS AND MATERIALS
To prepare this paper and fulfill our goals, different search engines (e.g., GOOGLE SCHOLAR), Databases (e.g., MEDLINE), and websites (e.g., SCOPUS) were recruited to search and find effective papers and investigations. To reach this purpose, we tried with papers published in the English language with no limitation in time. The bibliometrics was exploited to check the quality of the collected publications.
RESULTS
Each TLR molecule has its own molecular and structural biology, coreceptor(s), and abilities which make them unique or a complementary portion of the others. These immunogenetic molecules have remarkable roles and are much more important in different sections of immune and nonimmune systems rather than that we understand to date.
CONCLUSION
TLRs are suitable targets for ligand-drug discovery strategies to establish new therapeutics in the fields of infectious and autoimmune diseases, cancers, and other inflammatory diseases and disorders.
Topics: Adaptive Immunity; Alarmins; Animals; Drug Discovery; Humans; Immunity, Innate; Pathogen-Associated Molecular Pattern Molecules; Protein Conformation; Structure-Activity Relationship; Toll-Like Receptors
PubMed: 34195298
DOI: 10.1155/2021/9914854 -
Cellular and Molecular Life Sciences :... Jun 2016Inflammasomes are multi-protein platforms that are organized in the cytosol to cope with pathogens and cellular stress. The pattern recognition receptors NLRP1, NLRP3,... (Review)
Review
Inflammasomes are multi-protein platforms that are organized in the cytosol to cope with pathogens and cellular stress. The pattern recognition receptors NLRP1, NLRP3, NLRC4, AIM2 and Pyrin all assemble canonical platforms for caspase-1 activation, while caspase-11-dependent inflammasomes respond to intracellular Gram-negative pathogens. Inflammasomes are chiefly known for their roles in maturation and secretion of the inflammatory cytokines interleukin-(IL)1β and IL18, but they can also induce regulated cell death. Activation of caspases 1 and 11 in myeloid cells can trigger pyroptosis, a lytic and inflammatory cell death mode. Pyroptosis has been implicated in secretion of IL1β, IL18 and intracellular alarmins. Akin to these factors, it may have beneficial roles in controlling pathogen replication, but become detrimental in the context of chronic autoinflammatory diseases. Inflammasomes are increasingly implicated in induction of additional regulated cell death modes such as pyronecrosis and apoptosis. In this review, we overview recent advances in inflammasome-associated cell death research, illustrating the polyvalent roles of these macromolecular platforms in regulated cell death signaling.
Topics: Alarmins; Animals; Apoptosis; Caspase 1; Caspases; Caspases, Initiator; Gram-Negative Bacteria; Humans; Inflammasomes; Inflammation; Interleukin-18; Interleukin-1beta; Mice; Mice, Knockout; Pyroptosis; Signal Transduction
PubMed: 27048821
DOI: 10.1007/s00018-016-2204-3 -
The Journal of Clinical Investigation Aug 2018The biological basis of human aging remains one of the greatest unanswered scientific questions. Increasing evidence, however, points to a role for alterations in... (Review)
Review
The biological basis of human aging remains one of the greatest unanswered scientific questions. Increasing evidence, however, points to a role for alterations in mitochondrial function as a potential central regulator of the aging process. Here, we focus primarily on three aspects of mitochondrial biology that link this ancient organelle to how and why we age. In particular, we discuss the role of mitochondria in regulating the innate immune system, the mechanisms linking mitochondrial quality control to age-dependent pathology, and the possibility that mitochondrial-to-nuclear signaling might regulate the rate of aging.
Topics: Aging; Alarmins; Animals; Cell Nucleus; DNA, Mitochondrial; Humans; Immunity, Innate; Inflammation; Mitochondria; Mitophagy; Models, Immunological; Signal Transduction
PubMed: 30059016
DOI: 10.1172/JCI120842 -
Experimental & Molecular Medicine Dec 2020Damage-associated molecular patterns (DAMPs) are danger signals (or alarmins) alerting immune cells through pattern recognition receptors (PRRs) to begin defense... (Review)
Review
Damage-associated molecular patterns (DAMPs) are danger signals (or alarmins) alerting immune cells through pattern recognition receptors (PRRs) to begin defense activity. Moreover, DAMPs are host biomolecules that can initiate a noninflammatory response to infection, and pathogen-associated molecular pattern (PAMPs) perpetuate the inflammatory response to infection. Many DAMPs are proteins that have defined intracellular functions and are released from dying cells after tissue injury or chemo-/radiotherapy. In the tumor microenvironment, DAMPs can be ligands for Toll-like receptors (TLRs) expressed on immune cells and induce cytokine production and T-cell activation. Moreover, DAMPs released from tumor cells can directly activate tumor-expressed TLRs that induce chemoresistance, migration, invasion, and metastasis. Furthermore, DAMP-induced chronic inflammation in the tumor microenvironment causes an increase in immunosuppressive populations, such as M2 macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). Therefore, regulation of DAMP proteins can reduce excessive inflammation to create an immunogenic tumor microenvironment. Here, we review tumor-derived DAMP proteins as ligands of TLRs and discuss their association with immune cells, tumors, and the composition of the tumor microenvironment.
Topics: Alarmins; Animals; Biomarkers, Tumor; Disease Susceptibility; Gene Expression Regulation, Neoplastic; Humans; Immunomodulation; Neoplasm Proteins; Neoplasms; Organ Specificity; Protein Binding; Signal Transduction; Toll-Like Receptors; Tumor Microenvironment
PubMed: 33299138
DOI: 10.1038/s12276-020-00540-4 -
Apoptosis : An International Journal on... Oct 2017When apoptotic cells are not cleared in an efficient and timely manner, they progress to secondary necrosis and lose their membrane integrity. This results in a leakage... (Review)
Review
When apoptotic cells are not cleared in an efficient and timely manner, they progress to secondary necrosis and lose their membrane integrity. This results in a leakage of immunostimulatory, danger associated molecular patterns (DAMPs), similar to accidental (or primary) necrosis. However, primary necrosis is a sudden event with an inadvertent release of almost unmodified DAMPs. Secondary necrotic cells, in contrast, have gone through various modifications during the process of apoptosis. Recent research revealed that the molecules released from the cytoplasm or exposed on the cell surface differ between primary necrosis, secondary necrosis, and regulated necrosis such as necroptosis. This review gives an overview of these differences and focusses their effects on the immune response. The implications to human physiology and diseases are manifold and will be discussed in the context of cancer, neurodegenerative disorders and autoimmunity.
Topics: Alarmins; Animals; Apoptosis; Cell Death; Humans; Immunotherapy; Inflammation; Necrosis; Phagocytosis; Signal Transduction
PubMed: 28861714
DOI: 10.1007/s10495-017-1413-z -
European Journal of Immunology Apr 2023Epithelial cytokines are involved in the orchestration of T1/T2 inflammatory patterns. We question the persistence of this trait in air-liquid interface (ALI) epithelial...
Epithelial cytokines are involved in the orchestration of T1/T2 inflammatory patterns. We question the persistence of this trait in air-liquid interface (ALI) epithelial cultures and whether this local orientation can be related to systemic patterns (e.g., blood eosinophil counts [BECs]). We investigated alarmin release related to high versus low T2 phenotypes associated with chronic airway diseases. ALIs were reconstituted from 32 control, 40 chronic obstructive pulmonary disease, and 20 asthmatic patients. Interleukin-8 (IL-8; a T1-cytokine), IL-25, IL-33, and thymic stromal lymphopoietin (T2-alarmins) concentrations were assessed in subnatants at steady state and used to explain blood neutrophil and eosinophil counts. IL-25 and IL-8 levels were highest in asthma ALI-subnatants, whereas IL-33 was sparsely detected. Thymic stromal lymphopoietin levels were similar among groups. All asthma cell cultures were T1-high/T2-high, while chronic obstructive pulmonary disease and controls tended to be mixed. BECs were independently explained by both disease and in-culture T2-alarmin levels, irrespective of the T2-alarmin considered. The epithelial ALI-T2 signature was more frequently high in patients with a BEC > 300/mm . Despite removal from an in vivo environment for ≥2 months, ALIs release disease-specific cytokine "cocktails" into their subnatants, suggesting continued persistence of alarmin orientation in differentiated cell line environments.
Topics: Humans; Alarmins; Interleukin-33; Eosinophils; Interleukin-8; Cytokines; Asthma; Thymic Stromal Lymphopoietin; Pulmonary Disease, Chronic Obstructive
PubMed: 36793156
DOI: 10.1002/eji.202250101 -
The Journal of Experimental Medicine Jun 2024Epithelium-derived cytokines or alarmins, such as interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP), are major players in type 2 immunity and asthma. Here,...
Epithelium-derived cytokines or alarmins, such as interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP), are major players in type 2 immunity and asthma. Here, we demonstrate that TNF-like ligand 1A (TL1A) is an epithelial alarmin, constitutively expressed in alveolar epithelium at steady state in both mice and humans, which cooperates with IL-33 for early induction of IL-9high ILC2s during the initiation of allergic airway inflammation. Upon synergistic activation by IL-33 and TL1A, lung ILC2s acquire a transient IL-9highGATA3low "ILC9" phenotype and produce prodigious amounts of IL-9. A combination of large-scale proteomic analyses, lung intravital microscopy, and adoptive transfer of ILC9 cells revealed that high IL-9 expression distinguishes a multicytokine-producing state-of-activated ILC2s with an increased capacity to initiate IL-5-dependent allergic airway inflammation. Similar to IL-33 and TSLP, TL1A is expressed in airway basal cells in healthy and asthmatic human lungs. Together, these results indicate that TL1A is an epithelium-derived cytokine and an important cofactor of IL-33 in the airways.
Topics: Animals; Humans; Mice; Alarmins; Asthma; Cytokines; Immunity, Innate; Inflammation; Interleukin-33; Interleukin-9; Lymphocytes; Proteomics
PubMed: 38597952
DOI: 10.1084/jem.20231236 -
Nature Communications Oct 2022HIV-1 eradication is hindered by viral persistence in cell reservoirs, established not only in circulatory CD4T-cells but also in tissue-resident macrophages. The nature...
HIV-1 eradication is hindered by viral persistence in cell reservoirs, established not only in circulatory CD4T-cells but also in tissue-resident macrophages. The nature of macrophage reservoirs and mechanisms of persistence despite combined anti-retroviral therapy (cART) remain unclear. Using genital mucosa from cART-suppressed HIV-1-infected individuals, we evaluated the implication of macrophage immunometabolic pathways in HIV-1 persistence. We demonstrate that ex vivo, macrophage tissue reservoirs contain transcriptionally active HIV-1 and viral particles accumulated in virus-containing compartments, and harbor an inflammatory IL-1RS100A8MMP7M4-phenotype prone to glycolysis. Reactivation of infectious virus production and release from these reservoirs in vitro are induced by the alarmin S100A8, an endogenous factor produced by M4-macrophages and implicated in "sterile" inflammation. This process metabolically depends on glycolysis. Altogether, inflammatory M4-macrophages form a major tissue reservoir of replication-competent HIV-1, which reactivate viral production upon autocrine/paracrine S100A8-mediated glycolytic stimulation. This HIV-1 persistence pathway needs to be targeted in future HIV eradication strategies.
Topics: Alarmins; Anti-Retroviral Agents; CD4-Positive T-Lymphocytes; Calgranulin A; HIV Infections; HIV-1; Humans; Macrophages; Matrix Metalloproteinase 7; Virus Latency; Virus Replication
PubMed: 36220814
DOI: 10.1038/s41467-022-33401-x -
Journal of Leukocyte Biology Jul 2019The oral cavity is a unique environment containing teeth juxtaposed with soft tissues, all of which are constantly bathed in microbial products and host-derived factors.... (Review)
Review
The oral cavity is a unique environment containing teeth juxtaposed with soft tissues, all of which are constantly bathed in microbial products and host-derived factors. While microbial dysbiosis in the oral cavity clearly leads to oral inflammatory disease, recent advances find that endogenous danger-associated molecular patterns (DAMPs) released from oral and salivary tissue also contribute to the progression of inflammatory and autoimmune disease, respectively. In contrast, DAMPs produced during oral fungal infection actually promote the resolution of infection. Here, we present a review of the literature suggesting a role for signaling by DAMPs, which may intersect with pathogen-associated molecular pattern (PAMP) signaling, in diseases that manifest in the oral cavity, specifically periodontal disease, oropharyngeal candidiasis, and Sjögren's syndrome.
Topics: Alarmins; Candidiasis, Oral; Extracellular Traps; Humans; Pathogen-Associated Molecular Pattern Molecules; Periodontal Diseases; Signal Transduction; Sjogren's Syndrome
PubMed: 30776147
DOI: 10.1002/JLB.4MIR1118-439R