Molecular half-full mechanisms by phagocityc cells on invasive Aspergilosis
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Fungus from the Aspergillus genus mainly affects lung tissue, occurring when the integrity of the host immune system is compromised. The human body uses immunocompetence conditions from mechanical and enzymatic defenses and the action of the innate immune system cells and also uses adaptive responses to control infection. Neutrophils, macrophages, and dendritic cells are critical as antifungal effector cells possess surface receptors that recognize fungal structures and trigger specific responses. TLRs and Dectin-1 the most studied for this interaction. TLRs are responsible for the production and release of cytokines and Dectin-1 is essential in the phagocytosis of the particle recognition and production of ROS. The best-studied cytokines and its crucial role in the response to Aspergillus spp. are TNF-α, IFN-γ, and IL-12. In this work, we reviewed the main mechanisms related to molecular receptors on phagocytic cells involved in the recognition of Aspergillus spp. Understanding the immune response in situations of immunocompetence and its comparison in immunodeficient organisms could provide alternatives to control invasive aspergillosis.Keywords:
Immunocompetence
Immune Recognition
Innate lymphoid cell
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TLR ligands are present on both commensal and pathogenic microbes. Intestinal epithelial cells (IECs) have been observed to be largely unresponsive to TLR ligands. This observation has partly been explained by the fact that TLR expression on IECs is sparse. The discovery of the Toll-like receptors finally identified the innate immune receptors that were responsible for many of the innate immune functions that had been studied for many years. Interestingly, TLRs seem only to be involved in the cytokine production and cellular activation in response to microbes, and do not play a significant role in the adhesion and phagocytosis of microorganisms. One member of this group, interleukin-1β (IL-1β), together with tumour-necrosis factor (TNF), is defined as an 'alarm cytokine'. It is secreted by macrophages and initiates inflammation on activation of TLRs. Keywords: Toll-like receptors, inflammation, commensal bacteria, cytokine, TLRs, TLR ligands, tumour-necrosis factor (TNF), alarm cytokine, expression of TLR, MyD88-Dependent Signaling, MyD88-Independent Signaling, TLR Signaling Pathways, Various Type of TLRs, Commensal Bacteria and TLR
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β-Glucans are structural components of fungal cell walls, which have a stimulatory effect on the immune system. Although a number of receptors for these carbohydrates have been proposed, the recently identified C-type lectin-like receptor, Dectin-1, appears to play a central role. Dectin-1 is expressed on phagocytic cells, including macrophages and neutrophils, and mediates both the internalization and cellular responses to β-glucan, through unique mechanisms. Dectin-1 can recognize and respond to live fungal pathogens and is being increasingly appreciated as having a key role in the innate responses to these pathogens. In addition to its exogenous ligands, Dectin-1 can recognize an unidentified endogenous ligand on T cells and may act as a co-stimulatory molecule, although its function in these responses is less clear. This review will highlight the current knowledge of Dectin-1 and its potential role in antifungal immunity, as well as deficiencies in our understanding.
Internalization
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Immune receptor
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The eradication of tumor cells requires communication to and signaling by cells of the immune system. Natural killer (NK) cells are essential tumor-killing effector cells of the innate immune system; however, little is known about whether or how other immune cells recognize tumor cells to assist NK cells. Here, we show that the innate immune receptor Dectin-1 expressed on dendritic cells and macrophages is critical to NK-mediated killing of tumor cells that express N-glycan structures at high levels. Receptor recognition of these tumor cells causes the activation of the IRF5 transcription factor and downstream gene induction for the full-blown tumoricidal activity of NK cells. Consistent with this, we show exacerbated in vivo tumor growth in mice genetically deficient in either Dectin-1 or IRF5. The critical contribution of Dectin-1 in the recognition of and signaling by tumor cells may offer new insight into the anti-tumor immune system with therapeutic implications.
NK-92
Innate lymphoid cell
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Toll-like receptors (TLRs) are widely expressed in the innate and adaptive immune system. They initiate host defense against endogenous and exogenous pathogens containing conserved pathogen associated molecular patterns. TLRs are critical bridges between the innate and adaptive immunity, especially the cellular immunity mediated by T cells. Emerging evidence indicated that B cells express almost all subtypes of TLRs. TLRs play critical role not only in regulation of proliferation, maturation and function of B cells, but also in pathogenesis of diseases, such as systemic lupus erythematosus and chronic lymphocytic leukemia. Targeting TLRs of B cells is a promising therapeutic strategy for these disorders.
Pathogenesis
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Toll-Like Receptors (TLRs) are critical mediators of the innate immune response and subsequent activation of adaptive immune responses to pathogens that invade the body. TLRs on immune cells are the basis of our multigenic, innate immune, inflammatory response to pathogenic signature molecules that cause tissue damage. Functional TLRs are expressed not only on immune cells, but also on non-immune cells including cancer cells. TLRs are critical mediators of cellular transformation, tumor progression, and metastasis.
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Many aspects of antimicrobial host responses are orchestrated by a complex network of cytokines and their receptors. This review focuses on recent progress in our understanding of the function of cytokines in innate immune responses to Aspergillus. TNF, a recognition cytokine, has been shown to be required for initiation of the innate response in the mouse model of invasive aspergillosis. Several recruitment cytokines play critical roles in mediating influx of specific leukocytes to the site of infection in invasive aspergillosis. Among these, the ELR+ subset of CXC chemokines and their receptor CXCR2 are critical to neutrophil recruitment, while CCL3/macrophage inflammatory protein (MIP)-1α and CCL2/monocyte chemoattractant protein (MCP)-1 are critical to recruitment of monocyte-lineage leukocytes and NK cells, respectively. Of the activation cytokines, those associated with the Th-1 phenotype, including interleukin (IL)-12, IL-18, and interferon-gamma (IFN-γ), are critical to protective responses to the infection. Conversely, the Th2-phenotype cytokines IL-4 and IL-10 contribute to progression of infection. Modulation of the immune response to Aspergillus by manipulating these mediators remains intriguing as a potential adjunctive treatment in patients with invasive aspergillosis.
Defence mechanisms
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The innate ability of macrophages to induce an immune response to pathogens is dependent upon germline encoded pattern recognition receptors which recognise conserved microbial structures. These receptors not only mediate pathogen recognition, but promote microbial uptake and killing and the induction of inflammatory responses. Although the recently described Toll-like receptors (TLR) have been shown to play a central role in mediating the intracellular signals involved, the non-TLRs also have important functions in these processes. Once such receptor is Dectin-1, a myeloid expressed signalling C-type lectin-like receptor which is involved in the innate recognition of fungal pathogens. Dectin-1 can induce a variety of cellular responses, including phagocytosis, the respiratory burst and cytokine production. These responses are mediated through novel signalling pathways induced from the cytoplasmic immuno-receptor tyrosine based activation-like motif of the receptor. Although the in vivo role of Dectin-1 has still to be fully elucidated, there is emerging evidence that this receptor plays a role in the inflammatory response to pulmonary fungal pathogens and that it is involved in certain autoimmune and respiratory diseases.
Immune receptor
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