scholarly journals Tissue-autonomous immune response regulates stress signalling during hypertrophy

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Robert Krautz ◽  
Dilan Khalili ◽  
Ulrich Theopold
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Salivary Glands ◽  
Feedback Loop ◽  
Mapk Pathway ◽  
Therapeutic Approaches ◽  
Jnk Pathway ◽  
Immune Effector ◽  
Tissue Integrity ◽  
Stress Signalling

Postmitotic tissues are incapable of replacing damaged cells through proliferation, but need to rely on buffering mechanisms to prevent tissue disintegration. By constitutively activating the Ras/MAPK-pathway via RasV12-overexpression in the postmitotic salivary glands of Drosophila larvae, we overrode the glands adaptability to growth signals and induced hypertrophy. The accompanied loss of tissue integrity, recognition by cellular immunity and cell death are all buffered by blocking stress signalling through a genuine tissue-autonomous immune response. This novel, spatio-temporally tightly regulated mechanism relies on the inhibition of a feedback-loop in the JNK-pathway by the immune effector and antimicrobial peptide Drosomycin. While this interaction might allow growing salivary glands to cope with temporary stress, continuous Drosomycin expression in RasV12-glands favors unrestricted hypertrophy. These findings indicate the necessity to refine therapeutic approaches that stimulate immune responses by acknowledging their possible, detrimental effects in damaged or stressed tissues.

scholarly journals Tissue-autonomous immune response regulates stress signalling during hypertrophy

2019 ◽  
Author(s):  
Robert Krautz ◽  
Dilan Khalili ◽  
Ulrich Theopold
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Stress Response ◽  
Immune Responses ◽  
Salivary Glands ◽  
Mapk Pathway ◽  
Therapeutic Approaches ◽  
Direct Inhibition ◽  
Systemic Immune Response ◽  
Stress Accumulation

AbstractPostmitotic tissues are incapable of replacing damaged cells through proliferation, but need to rely on buffering mechanisms to prevent tissue disintegration. By constitutively activating the Ras/MAPK-pathway via RasV12-overexpression in the postmitotic salivary glands of Drosophila larvae, we overrode the glands adaptability to growth signals, induced hypertrophy and stress accumulation. This allowed us to decipher a novel, spatio-temporally regulated interaction between the JNK-stress response and a genuine tissue-autonomous immune response. Central to this interaction is the direct inhibition of JNK-signalling by the antimicrobial peptide Drosomycin, which blocks programmed cell death and prevents recognition of the stressed tissue by the systemic immune response. While this mechanism might allow growing salivary glands to cope with temporary stress, continuous expression of Drosomycin favors survival of unrestricted, hypertrophic RasV12-glands. Our findings indicate the necessity for refined therapeutic approaches that fundamentally acknowledge detrimental effects that stimulated immune responses have on tissues coping with damage and stress.

scholarly journals JNK pathway restricts DENV, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands

2020 ◽  
Author(s):  
Avisha Chowdhury ◽  
Cassandra M. Modahl ◽  
Siok Thing Tan ◽  
Benjamin Wong Wei Xiang ◽  
Dorothée Missé ◽  
...  
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Salivary Glands ◽  
Antiviral Effect ◽  
Negative Regulator ◽  
Chikv Infection ◽  
Jnk Pathway ◽  
Antiviral Effects ◽  
Antiviral Function ◽  
Arbovirus Infection

AbstractArbovirus infection of Aedes aegypti salivary glands (SGs) determines transmission. However, there is a dearth of knowledge on SG immunity. Here, we characterized SG immune response to dengue, Zika and chikungunya viruses using high-throughput transcriptomics. The three viruses regulate components of Toll, IMD and JNK pathways. However, silencing of Toll and IMD components showed variable effects on SG infection by each virus. In contrast, regulation of JNK pathway produced consistent responses. Virus infection increased with depletion of component Kayak and decreased with depletion of negative regulator Puckered. Virus-induced JNK pathway regulates complement and apoptosis in SGs via TEP20 and Dronc, respectively. Individual and co-silencing of these genes demonstrate their antiviral effects and that both may function together. Co-silencing either TEP20 or Dronc with Puckered annihilates JNK pathway antiviral effect. We identified and characterized the broad antiviral function of JNK pathway in SGs, expanding the immune arsenal that blocks arbovirus transmission.

scholarly journals Unlocking the Potential of Vaccines Built on Messenger RNA

2021 ◽  
pp. 160-197
Author(s):  
Elena Locci ◽  
Silvia Raymond
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Side Effects ◽  
Immune Responses ◽  
Messenger Rna ◽  
Healthy Tissue ◽  
Therapeutic Approaches ◽  
Inflammatory Reactions ◽  
Discontinuation Of Treatment ◽  
Keywords Cancer

In recent years, immunotherapy has revolutionized the treatment of cancer; however, inflammatory reactions in healthy tissues often have side effects that can be serious and lead to permanent discontinuation of treatment. This toxicity is not yet well understood and is a major obstacle to the use of immunotherapy. When the immune system is so severely activated, the resulting inflammatory reaction can have detrimental effects and sometimes serious damage to healthy tissue. We wanted to know if there was a difference between an optimal immune response that aims to kill cancer and an unwanted response that could affect healthy tissue. Identifying the distinctive elements between these two immune responses allows the development of new, more effective and less toxic therapeutic approaches. Keywords: Cancer; Cells; Tissues, Tumors; Prevention, Prognosis; Diagnosis; Imaging; Screening; Treatment; Management

GLOBAL PROPERTIES OF A MODEL OF IMMUNE EFFECTOR RESPONSES TO VIRAL INFECTIONS

2007 ◽  
Vol 10 (04) ◽  
pp. 495-503 ◽  
Author(s):  
XIA WANG ◽  
XINYU SONG
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Lyapunov Functions ◽  
Viral Infections ◽  
Reproductive Number ◽  
Asymptotically Stable ◽  
Globally Asymptotically Stable ◽  
Immune Effector ◽  
Global Properties ◽  
Ctl Immune Response

This article proposes a mathematical model which has been used to investigate the importance of lytic and non-lytic immune responses for the control of viral infections. By means of Lyapunov functions, the global properties of the model are obtained. The virus is cleared if the basic reproduction number R0 ≤ 1 and the virus persists in the host if R0 > 1. Furthermore, if R0 > 1 and other conditions hold, the immune-free equilibrium E0 is globally asymptotically stable. The equilibrium E1 exists and is globally asymptotically stale if the CTL immune response reproductive number R1 < 1 and the antibody immune response reproductive number R2 > 1. The equilibrium E2 exists and is globally asymptotically stable if R1 > 1 and R2 < 1. Finally, the endemic equilibrium E3 exists and is globally asymptotically stable if R1 > 1 and R2 > 1.

scholarly journals Type I and II Interferons in the Anti-Tumor Immune Response

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1037
Author(s):  
Sarah E. Fenton ◽  
Diana Saleiro ◽  
Leonidas C. Platanias
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Tumor Response ◽  
Cancer Surveillance ◽  
Type I ◽  
Type Ii ◽  
Malignant Cells ◽  
Therapeutic Approaches ◽  
Feedback Mechanisms ◽  
Essential Components

The interferons (IFNs) are essential components of the immune response against infections and malignancies. IFNs are potent promoters of the anti-tumor response, but there is also evidence that feedback mechanisms regulated by IFNs negatively control immune responses to avoid hyper-activation and limit inflammation. This balance of responses plays an important role in cancer surveillance, immunoediting and response to anticancer therapeutic approaches. Here we review the roles of both type I and type II IFNs on the control of the immune response against malignancies in the context of effects on both malignant cells and cells of the immune system in the tumor microenvironment.

scholarly journals Mechanobiological Principles Influence the Immune Response in Regeneration: Implications for Bone Healing

2021 ◽  
Vol 9 ◽  
Author(s):  
Raphael S. Knecht ◽  
Christian H. Bucher ◽  
Sophie Van Linthout ◽  
Carsten Tschöpe ◽  
Katharina Schmidt-Bleek ◽  
...  
Keyword(s):  
Immune Response ◽  
Extracellular Matrix ◽  
Immune Responses ◽  
Tissue Regeneration ◽  
Immune Cells ◽  
Material Properties ◽  
Treatment Options ◽  
Hematopoietic Cells ◽  
Therapeutic Approaches ◽  
New Treatment

A misdirected or imbalanced local immune composition is often one of the reasons for unsuccessful regeneration resulting in scarring or fibrosis. Successful healing requires a balanced initiation and a timely down-regulation of the inflammation for the re-establishment of a biologically and mechanically homeostasis. While biomaterial-based approaches to control local immune responses are emerging as potential new treatment options, the extent to which biophysical material properties themselves play a role in modulating a local immune niche response has so far been considered only occasionally. The communication loop between extracellular matrix, non-hematopoietic cells, and immune cells seems to be specifically sensitive to mechanical cues and appears to play a role in the initiation and promotion of a local inflammatory setting. In this review, we focus on the crosstalk between ECM and its mechanical triggers and how they impact immune cells and non-hematopoietic cells and their crosstalk during tissue regeneration. We realized that especially mechanosensitive receptors such as TRPV4 and PIEZO1 and the mechanosensitive transcription factor YAP/TAZ are essential to regeneration in various organ settings. This indicates novel opportunities for therapeutic approaches to improve tissue regeneration, based on the immune-mechanical principles found in bone but also lung, heart, and skin.

scholarly journals Overcoming Immune Depletion is the Main Goal of Developing New Therapies

2021 ◽  
pp. 141-181
Author(s):  
Ricardo Gobato ◽  
Abhijit Mitra
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Side Effects ◽  
Immune Responses ◽  
Inflammatory Reaction ◽  
Healthy Tissue ◽  
Therapeutic Approaches ◽  
Inflammatory Reactions ◽  
Discontinuation Of Treatment ◽  
Keywords Cancer

In recent years, immunotherapy has revolutionized the treatment of cancer; However, inflammatory reactions in healthy tissues often have side effects that can be serious and lead to permanent discontinuation of treatment. This toxicity is not yet well understood and is a major obstacle to the use of immunotherapy. When the immune system is so severely activated, the resulting inflammatory reaction can have detrimental effects and sometimes serious damage to healthy tissue. We wanted to know if there was a difference between an optimal immune response that aims to kill cancer and an unwanted response that could affect healthy tissue. Identifying the distinctive elements between these two immune responses allows the development of new, more effective and less toxic therapeutic approaches. Keywords: Cancer; Cells; Tissues; Tumors; Prevention; Prognosis; Diagnosis; Imaging; Screening, Treatment; Management

Immune responses to Helicobacter pylori colonization: mechanisms and clinical outcomes

2006 ◽  
Vol 110 (3) ◽  
pp. 305-314 ◽  
Author(s):  
Cynthia Portal-Celhay ◽  
Guillermo I. Perez-Perez
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Immune Responses ◽  
Gastric Lymphoma ◽  
Gastric Epithelium ◽  
Immune Effector ◽  
Ulcer Disease ◽  
Gastroduodenal Disease ◽  
Increased Risk ◽  
H Pylori

Helicobacter pylori colonizes the stomachs of half of the world's population and usually persists in the gastric mucosa of human hosts for decades or life. Although most H. pylori-positive people are asymptomatic, the presence of H. pylori is associated with increased risk for the development of peptic ulcer disease, gastric adenocarcinoma and gastric lymphoma. The development of a sustained gastric inflammatory and immune response to infection appears to be pivotal for the development of disease. During its long co-existence with humans, H. pylori has evolved complex strategies to maintain a mild inflammation of the gastric epithelium while limiting the extent of immune effector activity. In this review, the nature of the host immune response to H. pylori infection and the mechanism employed by the bacterium to evade them is considered. Understanding the mechanisms of colonization, persistence and virulence factors of the bacterium as well as the innate and adaptive immune responses of the host are critically important for the development of new strategies to prevent the development of H. pylori-induced gastroduodenal disease.

scholarly journals Concomitant infections, parasites and immune responses

Parasitology ◽  
2001 ◽  
Vol 122 (S1) ◽  
pp. S23-S38 ◽  
Author(s):  
F. E. G. COX
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
The Other ◽  
Clinical Disease ◽  
Mixed Infections ◽  
Infectious Agents ◽  
Cytokine Network ◽  
Immune Effector ◽  
Effector Molecules

Concomitant infections are common in nature and often involve parasites. A number of examples of the interactions between protozoa and viruses, protozoa and bacteria, protozoa and other protozoa, protozoa and helminths, helminths and viruses, helminths and bacteria, and helminths and other helminths are described. In mixed infections the burden of one or both the infectious agents may be increased, one or both may be suppressed or one may be increased and the other suppressed. It is now possible to explain many of these interactions in terms of the effects parasites have on the immune system, particularly parasite-induced immunodepression, and the effects of cytokines controlling polarization to the Th1or Th2arms of the immune response. In addition, parasites may be affected, directly or indirectly, by cytokines and other immune effector molecules and parasites may themselves produce factors that affect the cells of the immune system. Parasites are, therefore, affected when they themselves, or other organisms, interact with the immune response and, in particular, the cytokine network. The importance of such interactions is discussed in relation to clinical disease and the development and use of vaccines.

scholarly journals Messing with the Sentinels—The Interaction of Staphylococcus aureus with Dendritic Cells

2018 ◽  
Vol 6 (3) ◽  
pp. 87 ◽  
Author(s):  
Murthy Darisipudi ◽  
Maria Nordengrün ◽  
Barbara Bröker ◽  
Vincent Péton
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Respiratory Diseases ◽  
Adaptive Immune Responses ◽  
Immune Effector ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Aureus Infection

Staphylococcus aureus (S. aureus) is a dangerous pathogen as well as a frequent colonizer, threatening human health worldwide. Protection against S. aureus infection is challenging, as the bacteria have sophisticated strategies to escape the host immune response. To maintain equilibrium with S. aureus, both innate and adaptive immune effector mechanisms are required. Dendritic cells (DCs) are critical players at the interface between the two arms of the immune system, indispensable for inducing specific T cell responses. In this review, we highlight the importance of DCs in mounting innate as well as adaptive immune responses against S. aureus with emphasis on their role in S. aureus-induced respiratory diseases. We also review what is known about mechanisms that S. aureus has adopted to evade DCs or manipulate these cells to its advantage.

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