scholarly journals The Emerging Role of Complement Lectin Pathway in Trypanosomatids: Molecular Bases in Activation, Genetic Deficiencies, Susceptibility to Infection, and Complement System-Based Therapeutics

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Ingrid Evans-Osses ◽  
Iara de Messias-Reason ◽  
Marcel I. Ramirez
Keyword(s):  
Host Defense ◽  
Complement System ◽  
Innate Immune ◽  
Lectin Pathway ◽  
Complement Factors ◽  
Susceptibility To Infection ◽  
Host Defense System ◽  
Molecular Patterns ◽  
Molecular Components ◽  
Mannan Binding Lectin

The innate immune system is evolutionary and ancient and is the pivotal line of the host defense system to protect against invading pathogens and abnormal self-derived components. Cellular and molecular components are involved in recognition and effector mechanisms for a successful innate immune response. The complement lectin pathway (CLP) was discovered in 1990. These new components at the complement world are very efficient. Mannan-binding lectin (MBL) and ficolin not only recognize many molecular patterns of pathogens rapidly to activate complement but also display several strategies to evade innate immunity. Many studies have shown a relation between the deficit of complement factors and susceptibility to infection. The recently discovered CLP was shown to be important in host defense against protozoan microbes. Although the recognition of pathogen-associated molecular patterns by MBL and Ficolins reveal efficient complement activations, an increase in deficiency of complement factors and diversity of parasite strategies of immune evasion demonstrate the unsuccessful effort to control the infection. In the present paper, we will discuss basic aspects of complement activation, the structure of the lectin pathway components, genetic deficiency of complement factors, and new therapeutic opportunities to target the complement system to control infection.

Differential gene expressions of NLRC5 signaling pathway in chicken macrophages cells response to Salmonella Enteritidisderived lipopplysaccharides stimulation

2016 ◽  
Author(s):  
Guobin Chang ◽  
Lingling Qiu ◽  
Xiangping Liu ◽  
Zhiteng Li ◽  
Wei Lu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Host Defense ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Innate Immune ◽  
Gene Expressions ◽  
Mhc I ◽  
Chicken Macrophage ◽  
Differential Gene ◽  
Molecular Patterns

As we all known, NLRC5 recognizes intracellular pathogen-associated molecular patterns (PAMPs) and provokes innate immune system. Its role in innate immune response, NF-kB activation and MHC-I expression remains controversial. In the present study, it was detected that differential gene expressions in NLRC5 signaling pathway at 2, 4, 6 and 8 hours after exposure to LPS using qRT-PCR technology, then analyzed its roles in host defense. The results showed that, comparing to control groups, the expression of NLRC5, MHC-I and IL-18 in LPS-treated groups were significantly up-regulated at 2 hours post stimulation (hps), TLR4 and NF-kB showed conspicuously up-regulated at 4 hps, while STAT1 was significantly down-regulated at 8 hps. Collectively, LPS did evoke inflammatory responses and NLRC5 may negatively regulate NF-kB and critically regulate MHC-I to control intracellular PAMPs in chicken macrophage cell line but the specific role of NLRC5 in host defense relates to cell types and species tested.

scholarly journals Diabetes Is Associated with Increased Autoreactivity of Mannan-Binding Lectin

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Esben Axelgaard ◽  
Jakob Appel Østergaard ◽  
Steffen Thiel ◽  
Troels Krarup Hansen
Keyword(s):  
Diabetic Nephropathy ◽  
Complement System ◽  
Knockout Mice ◽  
Ex Vivo ◽  
Lectin Pathway ◽  
Urine Albumin ◽  
Mannan Binding Lectin ◽  
The Complement System ◽  
Binding Lectin

Mannan-binding lectin (MBL) has been reported to be involved in the pathophysiology of diabetic nephropathy. MBL is a pattern-recognition molecule of the innate immune system that initiates the lectin pathway of the complement system upon recognition of evolutionary conserved pathogen-associated molecular patterns or to altered self-tissue. Our group have previously shown direct effects of MBL on diabetes-induced kidney damage, and we hypothesized that MBL may cause autoactivation of the complement system via binding to neoepitopes induced by hyperglycemia. In the present study, we induced diabetes in MBL knockout mice and in wild type C57BL/6J mice by low-dose streptozotocin injection and measured blood glucose and urine albumin-to-creatinine ratio to monitor development of diabetes. After 24 weeks, fluorescently labelled recombinant MBL was injected intravenously in diabetic MBL knockout mice after which the distribution was investigated using in vivo fluorescence imaging. Mice were subjected to in vivo and ex vivo imaging 24 hours after injection. MBL was found to accumulate in the kidneys of diabetic mice as compared to healthy control mice (p<0.0001). These findings support the hypothesis of a significant role of MBL and the complement system in the pathophysiology of diabetic nephropathy.

scholarly journals Human IgA Activates the Complement System Via the Mannan-Binding Lectin Pathway

2001 ◽  
Vol 167 (5) ◽  
pp. 2861-2868 ◽  
Author(s):  
Anja Roos ◽  
Lee H. Bouwman ◽  
Daniëlle J. van Gijlswijk-Janssen ◽  
Maria C. Faber-Krol ◽  
Gregory L. Stahl ◽  
...  
Keyword(s):  
Complement System ◽  
Lectin Pathway ◽  
Mannan Binding Lectin ◽  
The Complement System ◽  
Binding Lectin

scholarly journals Increased Autoreactivity of the Complement-Activating Molecule Mannan-Binding Lectin in a Type 1 Diabetes Model

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jakob Appel Østergaard ◽  
Marieta Milkova Ruseva ◽  
Talat Habib Malik ◽  
Ingeborg Torp Hoffmann-Petersen ◽  
Matthew Caleb Pickering ◽  
...  
Keyword(s):  
Complement System ◽  
Drug Targets ◽  
Lectin Pathway ◽  
Diabetes Model ◽  
Healthy Control ◽  
End Stage ◽  
Mannan Binding Lectin ◽  
The Complement System ◽  
Binding Lectin ◽  
Immunofluorescence Intensity

Background. Diabetic kidney disease is the leading cause of end-stage renal failure despite intensive treatment of modifiable risk factors. Identification of new drug targets is therefore of paramount importance. The complement system is emerging as a potential new target. The lectin pathway of the complement system, initiated by the carbohydrate-recognition molecule mannan-binding lectin (MBL), is linked to poor kidney prognosis in diabetes. We hypothesized that MBL activates complement upon binding within the diabetic glomerulus.Methods. We investigated this by comparing complement deposition and activation in kidneys from streptozotocin-induced diabetic mice and healthy control mice.Results. After 20 weeks of diabetes, glomerular deposition of MBL was significantly increased. Diabetic animals had 2.0-fold higher (95% CI 1.6–2.5) immunofluorescence intensity from anti-MBL antibodies compared with controls (P<0.001). Diabetes and control groups did not differ in glomerular immunofluorescence intensity obtained by antibodies against complement factors C4, C3, and C9. However, the circulating complement activation product C3a was increased in diabetes as compared to control mice (P=0.04).Conclusion. 20 weeks of diabetes increased MBL autoreactivity in the kidney and circulating C3a concentration. Together with previous findings, these results indicate direct effects of MBL within the kidney in diabetes.

The mannan-binding-lectin pathway of the innate immune response

2001 ◽  
Vol 13 (1) ◽  
pp. 74-78 ◽  
Author(s):  
Mihaela Gadjeva ◽  
Steffen Thiel ◽  
Jens C Jensenius
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Lectin Pathway ◽  
Mannan Binding Lectin ◽  
Binding Lectin

scholarly journals OSTEOARTHRITIS AND IMMUNITY

2021 ◽  
Vol 29 (1) ◽  
pp. 44-51
Author(s):  
Irina Momcheva ◽  
I. Kazmin ◽  
S. Hristova ◽  
V. Madjova
Keyword(s):  
Complement System ◽  
Cell Membranes ◽  
Cartilage Damage ◽  
Joint Damage ◽  
Innate Immune ◽  
Low Grade ◽  
Complement Receptors ◽  
Molecular Patterns ◽  
Low Grade Inflammation ◽  
The Complement System

Abstract         Low-grade inflammation is part of the pathogenesis of osteoarthritis (OA) from its earliest stages and contributes to the acceleration of the degenerative process. Innate immunity has a leading role in it.        Activation of the innate immune response is initiated by stimulation of the receptors on the cell membrane to recognize the secreted PAMPs (pathogen-associated molecular patterns). However, PAMPs can also be activated by endogenous damage-related molecular patterns (DAMPs). The group of DAMPs also includes toll-like receptors (TLRs).The disruption of matrix homeostasis in the course of OA is an example of activation of these receptors in chronic damage.      The complement system is a key element of the innate immune system. It is one of the serum enzyme systems whose function is to opsonize antigens. The complement receptors on the surface of the cell membranes adhere to the targets for phagocytosis. The C3R fraction activates the complement cascade itself, as well as the oxygen metabolism of the cell, which is essential for the phagocytosis. The cartilage damage products released during joint damage are a separate class of potent complement modulators.     Complement fractions bind to complement receptors on the surface of the chondrocyte and the synoviocyte cell membranes by TLR. The complement system is involved in many processes in the course of osteoarthritis: chondrocyte degeneration, ECM degradation, low-grade inflammation in the osteoarthritis, cell lysis, unbalanced bone remodeling, osteophyte formation, and neoangiogenesis. Whether drug control of complement activation may be a future therapeutic strategy in the treatment of OA and prevent its progression is a subject of future studies.

scholarly journals Inflammasome and Cognitive Symptoms in Human Diseases: Biological Evidence from Experimental Research

2020 ◽  
Vol 21 (3) ◽  
pp. 1103 ◽  
Author(s):  
So Yeong Cheon ◽  
Jeongmin Kim ◽  
So Yeon Kim ◽  
Eun Jung Kim ◽  
Bon-Nyeo Koo
Keyword(s):  
Drug Target ◽  
Critical Role ◽  
The Elderly ◽  
Innate Immune ◽  
Human Diseases ◽  
Cognitive Symptoms ◽  
Inflammasome Component ◽  
Host Defense System ◽  
Infectious Pathogen ◽  
Molecular Patterns

Cognitive symptoms are prevalent in the elderly and are associated with an elevated risk of developing dementia. Disease-driven changes can cause cognitive disabilities in memory, attention, and language. The inflammasome is an innate immune intracellular complex that has a critical role in the host defense system, in that it senses infectious pathogen-associated and endogenous danger-associated molecular patterns. An unbalanced or dysregulated inflammasome is associated with infectious, inflammatory, and neurodegenerative diseases. Due to its importance in such pathological conditions, the inflammasome is an emerging drug target for human diseases. A growing number of studies have revealed links between cognitive symptoms and the inflammasome. Several studies have shown that reducing the inflammasome component mitigates cognitive symptoms in diseased states. Therefore, understanding the inflammasome regulatory mechanisms may be required for the prevention and treatment of cognitive symptoms. The purpose of this review is to discuss the current understanding of the inflammasome and its relationships with cognitive symptoms in various human diseases.

scholarly journals Autophagy in Macrophages: Impacting Inflammation and Bacterial Infection

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Ali Vural ◽  
John H. Kehrl
Keyword(s):  
Immune Responses ◽  
Host Defense ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Transcriptional Networks ◽  
Dependent Manner ◽  
Innate Immune Responses ◽  
Rapid Induction ◽  
Downstream Effectors ◽  
Molecular Patterns

Macrophages are on the front line of host defense. They possess an array of germline-encoded pattern recognition receptors/sensors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and which activate downstream effectors/pathways to help mediate innate immune responses and host defense. Innate immune responses include the rapid induction of transcriptional networks that trigger the production of cytokines, chemokines, and cytotoxic molecules; the mobilization of cells including neutrophils and other leukocytes; the engulfment of pathogens by phagocytosis and their delivery to lysosome for degradation; and the induction of autophagy. Autophagy is a catabolic process that normally maintains cellular homeostasis in a lysosome-dependent manner, but it also functions as a cytoprotective response that intersects with a variety of general stress-response pathways. This review focuses on the intimately linked molecular mechanisms that help govern the autophagic pathway and macrophage innate immune responses.

scholarly journals A Plausible Role for Collectins in Skin Immune Homeostasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Tian Wang ◽  
Ke Li ◽  
Shengxiang Xiao ◽  
Yumin Xia
Keyword(s):  
Complement System ◽  
Skin Diseases ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Lectin Pathway ◽  
Immune Homeostasis ◽  
Innate Immune Responses ◽  
Mannose Binding ◽  
The Complement System ◽  
Complex Organ

The skin is a complex organ that faces the external environment and participates in the innate immune system. Skin immune homeostasis is necessary to defend against external microorganisms and to recover from stress to the skin. This homeostasis depends on interactions among a variety of cells, cytokines, and the complement system. Collectins belong to the lectin pathway of the complement system, and have various roles in innate immune responses. Mannose-binding lectin (MBL), collectin kidney 1, and liver (CL-K1, CL-L1) activate the lectin pathway, while all have multiple functions, including recognition of pathogens, opsonization of phagocytosis, and modulation of cytokine-mediated inflammatory responses. Certain collectins are localized in the skin, and their expressions change during skin diseases. In this review, we summarize important advances in our understanding of how MBL, surfactant proteins A and D, CL-L1, and CL-K1 function in skin immune homeostasis. Based on the potential roles of collectins in skin diseases, we suggest therapeutic strategies for skin diseases through the targeting of collectins and relevant regulators.

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