scholarly journals Schistosome-Derived Molecules as Modulating Actors of the Immune System and Promising Candidates to Treat Autoimmune and Inflammatory Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Luis Janssen ◽  
Gisele Lorranna Silva Santos ◽  
Herick Sampaio Muller ◽  
Anderson Rodrigues Araújo Vieira ◽  
Tatiana Amabile de Campos ◽  
...  
Keyword(s):  
Immune Responses ◽  
Defense Mechanisms ◽  
Inflammatory Diseases ◽  
Adaptive Responses ◽  
Immunomodulatory Effects ◽  
Larval Stages ◽  
Helminth Infections ◽  
Autoimmune And Inflammatory Diseases ◽  
Potential Applications ◽  
Parasite Infections

It is long known that some parasite infections are able to modulate specific pathways of host’s metabolism and immune responses. This modulation is not only important in order to understand the host-pathogen interactions and to develop treatments against the parasites themselves but also important in the development of treatments against autoimmune and inflammatory diseases. Throughout the life cycle of schistosomes the mammalian hosts are exposed to several biomolecules that are excreted/secreted from the parasite infective stage, named cercariae, from their tegument, present in adult and larval stages, and finally from their eggs. These molecules can induce the activation and modulation of innate and adaptive responses as well as enabling the evasion of the parasite from host defense mechanisms. Immunomodulatory effects of helminth infections and egg molecules are clear, as well as their ability to downregulate proinflammatory cytokines, upregulate anti-inflammatory cytokines, and drive a Th2 type of immune response. We believe that schistosomes can be used as a model to understand the potential applications of helminths and helminth-derived molecules against autoimmune and inflammatory diseases.

scholarly journals Viral-derived complement inhibitors: current status and potential role in immunomodulation

2016 ◽  
Vol 242 (4) ◽  
pp. 397-410 ◽  
Author(s):  
Hadi Abou-El-Hassan ◽  
Hassan Zaraket
Keyword(s):  
Complement System ◽  
Defense Mechanisms ◽  
Inflammatory Diseases ◽  
Immune Defense ◽  
Current Status ◽  
Viral Origin ◽  
Complement Proteins ◽  
Complement Inhibitors ◽  
Autoimmune And Inflammatory Diseases ◽  
The Complement System

The complement system is one of the body’s major innate immune defense mechanisms in vertebrates. Its function is to detect foreign bodies and promote their elimination through opsonisation or lysis. Complement proteins play an important role in the immunopathogenesis of several disorders. However, excessive complement activation does not confer more protection but instead leads to several autoimmune and inflammatory diseases. With inappropriate activation of the complement system, activated complement proteins and glycoproteins may damage both healthy and diseased tissues. Development of complement inhibitors represents an effective approach in controlling dysregulated complement activity and reducing disease severity, yet few studies have investigated the nature and role of novel complement inhibitory proteins of viral origin. Viral complement inhibitors have important implications in understanding the importance of complement inhibition and their role as a promising novel therapeutic approach in diseases caused by dysregulated complement function. In this review, we discuss the role and importance of complement inhibitors derived from several viruses in the scope of human inflammatory and autoimmune diseases.

scholarly journals Intestinal Microbes in Autoimmune and Inflammatory Disease

2020 ◽  
Vol 11 ◽  
Author(s):  
Wan-Jung H. Wu ◽  
Daniel F. Zegarra-Ruiz ◽  
Gretchen E. Diehl
Keyword(s):  
Genetic Variation ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Inflammatory Disease ◽  
Inflammatory Diseases ◽  
Current Evidence ◽  
Intestinal Microbes ◽  
Multiple Factors ◽  
Autoimmune And Inflammatory Diseases ◽  
Progression Of Disease

Autoimmune diseases and chronic inflammatory disorders are characterized by dysregulated immune responses resulting in excessive and uncontrolled tissue inflammation. Multiple factors including genetic variation, environmental stimuli, and infection are all thought to contribute to continued inflammation and pathology. Current evidence supports the microbiota as one such factor with emerging data linking commensal organisms to the onset and progression of disease. In this review, we will discuss links between the microbiota and specific diseases as well as highlight common pathways that link intestinal microbes with multiple autoimmune and inflammatory diseases.

scholarly journals Immunity against Helminths: Interactions with the Host and the Intercurrent Infections

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Emmanuelle Moreau ◽  
Alain Chauvin
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Chronic Infection ◽  
Inflammatory Diseases ◽  
Economic Importance ◽  
Host Immune System ◽  
Helminth Parasites ◽  
Strong Immune Response ◽  
Helminth Infections

Helminth parasites are of considerable medical and economic importance. Studies of the immune response against helminths are of great interest in understanding interactions between the host immune system and parasites. Effector immune mechanisms against tissue-dwelling helminths and helminths localized in the lumen of organs, and their regulation, are reviewed. Helminth infections are characterized by an association of Th2-like and Treg responses. Worms are able to persist in the host and are mainly responsible for chronic infection despite a strong immune response developed by the parasitized host. Two types of protection against the parasite, namely, premune and partial immunities, have been described. Immune responses against helminths can also participate in pathogenesis. Th2/Treg-like immunomodulation allows the survival of both host and parasite by controlling immunopathologic disorders and parasite persistence. Consequences of the modified Th2-like responses on co-infection, vaccination, and inflammatory diseases are discussed.

scholarly journals Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease

2020 ◽  
Vol 21 (3) ◽  
pp. 851 ◽  
Author(s):  
Vincent D. Giacalone ◽  
Camilla Margaroli ◽  
Marcus A. Mall ◽  
Rabindra Tirouvanziam
Keyword(s):  
Immune Responses ◽  
Defense Mechanisms ◽  
Inflammatory Diseases ◽  
Primary Response ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Neutrophilic Inflammation ◽  
Public Health Burden ◽  
Chronic Lung Diseases ◽  
New Concepts

Neutrophils have a prominent role in all human immune responses against any type of pathogen or stimulus. The lungs are a major neutrophil reservoir and neutrophilic inflammation is a primary response to both infectious and non-infectious challenges. While neutrophils are well known for their essential role in clearance of bacteria, they are also equipped with specific mechanisms to counter viruses and fungi. When these defense mechanisms become aberrantly activated in the absence of infection, this commonly results in debilitating chronic lung inflammation. Clearance of bacteria by phagocytosis is the hallmark role of neutrophils and has been studied extensively. New studies on neutrophil biology have revealed that this leukocyte subset is highly adaptable and fulfills diverse roles. Of special interest is how these adaptations can impact the outcome of an immune response in the lungs due to their potent capacity for clearing infection and causing damage to host tissue. The adaptability of neutrophils and their propensity to influence the outcome of immune responses implicates them as a much-needed target of future immunomodulatory therapies. This review highlights the recent advances elucidating the mechanisms of neutrophilic inflammation, with a focus on the lung environment due to the immense and growing public health burden of chronic lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), and acute lung inflammatory diseases such as transfusion-related acute lung injury (TRALI).

scholarly journals Protein phosphatases in TLR signaling

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Clovis H. T. Seumen ◽  
Tanja M. Grimm ◽  
Christof R. Hauck
Keyword(s):  
Immune Responses ◽  
Inflammatory Diseases ◽  
Protein Phosphatases ◽  
Innate Immune ◽  
Future Research ◽  
Tlr Signaling ◽  
Adaptive Immune ◽  
Innate Immune Signaling ◽  
Autoimmune And Inflammatory Diseases ◽  
Positive Regulators

AbstractToll-like receptors (TLRs) are critical sensors for the detection of potentially harmful microbes. They are instrumental in initiating innate and adaptive immune responses against pathogenic organisms. However, exaggerated activation of TLR receptor signaling can also be responsible for the onset of autoimmune and inflammatory diseases. While positive regulators of TLR signaling, such as protein serine/threonine kinases, have been studied intensively, only little is known about phosphatases, which counterbalance and limit TLR signaling. In this review, we summarize protein phosphorylation events and their roles in the TLR pathway and highlight the involvement of protein phosphatases as negative regulators at specific steps along the TLR-initiated signaling cascade. Then, we focus on individual phosphatase families, specify the function of individual enzymes in TLR signaling in more detail and give perspectives for future research. A better understanding of phosphatase-mediated regulation of TLR signaling could provide novel access points to mitigate excessive immune activation and to modulate innate immune signaling.

scholarly journals The cGAS-STING Pathway: A Promising Immunotherapy Target

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Ou ◽  
Ao Zhang ◽  
Yuxing Cheng ◽  
Ying Chen
Keyword(s):  
Innate Immunity ◽  
T Lymphocytes ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Signal Pathway ◽  
Autoimmune And Inflammatory Diseases ◽  
Immunotherapy Target ◽  
Sting Pathway

With the continuous development of immunotherapy, researchers have paid more attention to the specific immune regulatory mechanisms of various immune responses in different diseases. As a novel and vital innate immune signal pathway, the cGAS-STING signal pathway activated by nucleic acid substances, interplays with other immune responses, by which it participates in regulating cancer, autoimmune and inflammatory diseases, microbial and parasitic infectious diseases, and other diseases. With the exception of its role in innate immunity, the growing list of researches demonstrated expanding roles of the cGAS-STING signal pathway in bridging the innate immunity (macrophage polarization) with the adaptive immunity (T lymphocytes differentiation). Macrophages and T lymphocytes are the most representative cells of innate immunity and adaptive immunity, respectively. Their polarization or differentiation are involved in the pathogenesis and progression of various diseases. Here we mainly summarized recent advanced discoveries of how the cGAS-STING signal pathway regulated macrophages polarization and T lymphocytes differentiation in various diseases and vaccine applications, providing a promising direction for the development and clinical application of immunotherapeutic strategies for related diseases.

scholarly journals The Immuno-Modulation Effect of Macrophage-Derived Extracellular Vesicles in Chronic Inflammatory Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Xing ◽  
Xun Sun ◽  
Yiming Dou ◽  
Min Wang ◽  
Yanmei Zhao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Extracellular Vesicles ◽  
Inflammatory Diseases ◽  
Gastrointestinal Disease ◽  
Biological Functions ◽  
Modulation Effect ◽  
Chronic Inflammatory Diseases ◽  
Pathological Conditions ◽  
Potential Applications ◽  
Regulatory Effects

As natural nanocarriers and intercellular messengers, extracellular vesicles (EVs) control communication among cells. Under physiological and pathological conditions, EVs deliver generic information including proteins and nucleic acids to recipient cells and exert regulatory effects. Macrophages help mediate immune responses, and macrophage-derived EVs may play immunomodulatory roles in the progression of chronic inflammatory diseases. Furthermore, EVs derived from various macrophage phenotypes have different biological functions. In this review, we describe the pathophysiological significance of macrophage-derived extracellular vesicles in the development of chronic inflammatory diseases, including diabetes, cancer, cardiovascular disease, pulmonary disease, and gastrointestinal disease, and the potential applications of these EVs.

scholarly journals Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e040426
Author(s):  
Gyaviira Nkurunungi ◽  
Ludoviko Zirimenya ◽  
Jacent Nassuuna ◽  
Agnes Natukunda ◽  
Prossy N Kabuubi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Low Income ◽  
Controlled Trial ◽  
Interferon Γ ◽  
Population Differences ◽  
Vaccine Response ◽  
Vaccine Responses ◽  
Helminth Infections ◽  
Registration Number ◽  
Randomised Controlled

IntroductionSeveral licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response.Methods and analysisWe have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9–17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day ‘zero’; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses.Ethics and disseminationEthics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration numberISRCTN60517191.

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