scholarly journals The IκB-Protein BCL-3 Controls MAPK Activity by Promoting TPL-2 Degradation in the Nucleus

2018 ◽  
Author(s):  
Patricia E. Collins ◽  
Domenico Somma ◽  
David Kerrigan ◽  
Felicity Herrington ◽  
Karen R. Keeshan ◽  
...  
Keyword(s):  
Immune Cells ◽  
Innate Immune System ◽  
Molecular Mechanisms ◽  
Primary Site ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Nucleocytoplasmic Shuttling ◽  
Activation Threshold ◽  
Invasive Pathogens ◽  
Mapk Activity

AbstractThe ability of the innate immune system to distinguish between low level microbial presence and invasive pathogens is fundamental for immune homeostasis and immunity. However, the molecular mechanisms underlying threat discrimination by innate immune cells are not clearly defined. Here we describe the integration of the NF-ĸB and MAPK pathways in the nucleus by the IĸB protein BCL-3 and the MAP3K TPL-2. Our data reveals that TPL-2 is a nucleocytoplasmic shuttling protein and demonstrates that the nucleus is the primary site for TPL-2 ubiquitination and proteasomal degradation. BCL-3 promotes TPL-2 degradation through interaction in the nucleus. As a consequence, Bcl3-/- macrophages have increased TPL-2 stability and MAPK activity following TLR stimulation. The enhanced stability of TPL-2 in Bcl3-/- macrophages lowers the MAPK activation threshold and the level of TLR ligand required to initiate an inflammatory response. This study establishes the nucleus as a key regulatory site for TLR-induced MAPK activity and identifies BCL-3 as a regulator of the cellular decision to initiate inflammation

scholarly journals A Novel Regulatory Player in the Innate Immune System: Long Non-Coding RNAs

2021 ◽  
Vol 22 (17) ◽  
pp. 9535
Author(s):  
Yuhuai Xie ◽  
Yuanyuan Wei
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Innate Immune System ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Immune Mediated ◽  
Development And Differentiation ◽  
Non Coding Rnas ◽  
And Function

Long non-coding RNAs (lncRNAs) represent crucial transcriptional and post-transcriptional gene regulators during antimicrobial responses in the host innate immune system. Studies have shown that lncRNAs are expressed in a highly tissue- and cell-specific- manner and are involved in the differentiation and function of innate immune cells, as well as inflammatory and antiviral processes, through versatile molecular mechanisms. These lncRNAs function via the interactions with DNA, RNA, or protein in either cis or trans pattern, relying on their specific sequences or their transcriptions and processing. The dysregulation of lncRNA function is associated with various human non-infectious diseases, such as inflammatory bowel disease, cardiovascular diseases, and diabetes mellitus. Here, we provide an overview of the regulation and mechanisms of lncRNA function in the development and differentiation of innate immune cells, and during the activation or repression of innate immune responses. These elucidations might be beneficial for the development of therapeutic strategies targeting inflammatory and innate immune-mediated diseases.

scholarly journals BATF2 inhibits immunopathological Th17 responses by suppressing Il23a expression during Trypanosoma cruzi infection

2017 ◽  
Vol 214 (5) ◽  
pp. 1313-1331 ◽  
Author(s):  
Shoko Kitada ◽  
Hisako Kayama ◽  
Daisuke Okuzaki ◽  
Ritsuko Koga ◽  
Masao Kobayashi ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Parasite Burden ◽  
Innate Immune ◽  
Negative Regulator ◽  
Innate Immune Cells ◽  
Th17 Response ◽  
Ifn Γ ◽  
Cruzi Infection

Inappropriate IL-17 responses are implicated in chronic tissue inflammation. IL-23 contributes to Trypanosoma cruzi–specific IL-17 production, but the molecular mechanisms underlying regulation of the IL-23–IL-17 axis during T. cruzi infection are poorly understood. Here, we demonstrate a novel function of BATF2 as a negative regulator of Il23a in innate immune cells. IL-17, but not IFN-γ, was more highly produced by CD4+ T cells from spleens and livers of T. cruzi–infected Batf2−/− mice than by those of wild-type mice. In this context, Batf2−/− mice showed severe multiorgan pathology despite reduced parasite burden. T. cruzi–induced IL-23 production was increased in Batf2−/− innate immune cells. The T. cruzi–induced enhanced Th17 response was abrogated in Batf2−/−Il23a−/− mice. The interaction of BATF2 with c-JUN prevented c-JUN–ATF-2 complex formation, inhibiting Il23a expression. These results demonstrate that IFN-γ–inducible BATF2 in innate immune cells controls Th17-mediated immunopathology by suppressing IL-23 production during T. cruzi infection.

scholarly journals Immune cells—A curse and a blessing!

2021 ◽  
Vol 218 (6) ◽  
Author(s):  
Valbona Mirakaj
Keyword(s):  
Cardiovascular Disease ◽  
Immune System ◽  
Immune Cells ◽  
Innate Immune System ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
The Impact

Innate immune cells are crucial in the development and regulation of cardiovascular disease. In this issue, two groups, Davis et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20201839) and Li et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210008) describe the impact of the innate immune system on the development of cardiovascular disease.

scholarly journals Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2226
Author(s):  
Israa Shihab ◽  
Bariaa A. Khalil ◽  
Noha Mousaad Elemam ◽  
Ibrahim Y. Hachim ◽  
Mahmood Yaseen Hachim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Nk Cells ◽  
Immune Cells ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Cancer Microenvironment

The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy.

scholarly journals Stress Hyperglycemia, Insulin Treatment, and Innate Immune Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Fangming Xiu ◽  
Mile Stanojcic ◽  
Li Diao ◽  
Marc G. Jeschke
Keyword(s):  
Insulin Resistance ◽  
Innate Immunity ◽  
Immune System ◽  
Critical Illness ◽  
Immune Cells ◽  
Innate Immune System ◽  
Insulin Treatment ◽  
Innate Immune ◽  
Morbidity And Mortality ◽  
Innate Immune Cells

Hyperglycemia (HG) and insulin resistance are the hallmarks of a profoundly altered metabolism in critical illness resulting from the release of cortisol, catecholamines, and cytokines, as well as glucagon and growth hormone. Recent studies have proposed a fundamental role of the immune system towards the development of insulin resistance in traumatic patients. A comprehensive review of published literatures on the effects of hyperglycemia and insulin on innate immunity in critical illness was conducted. This review explored the interaction between the innate immune system and trauma-induced hypermetabolism, while providing greater insight into unraveling the relationship between innate immune cells and hyperglycemia. Critical illness substantially disturbs glucose metabolism resulting in a state of hyperglycemia. Alterations in glucose and insulin regulation affect the immune function of cellular components comprising the innate immunity system. Innate immune system dysfunction via hyperglycemia is associated with a higher morbidity and mortality in critical illness. Along with others, we hypothesize that reduction in morbidity and mortality observed in patients receiving insulin treatment is partially due to its effect on the attenuation of the immune response. However, there still remains substantial controversy regarding moderate versus intensive insulin treatment. Future studies need to determine the integrated effects of HG and insulin on the regulation of innate immunity in order to provide more effective insulin treatment regimen for these patients.

scholarly journals The Role of Macrophages in Staphylococcus aureus Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Grace R. Pidwill ◽  
Josie F. Gibson ◽  
Joby Cole ◽  
Stephen A. Renshaw ◽  
Simon J. Foster
Keyword(s):  
Staphylococcus Aureus ◽  
Immune System ◽  
Immune Cells ◽  
Innate Immune System ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Multiple Strategies ◽  
Aureus Infection ◽  
Opportunist Pathogen

Staphylococcus aureus is a member of the human commensal microflora that exists, apparently benignly, at multiple sites on the host. However, as an opportunist pathogen it can also cause a range of serious diseases. This requires an ability to circumvent the innate immune system to establish an infection. Professional phagocytes, primarily macrophages and neutrophils, are key innate immune cells which interact with S. aureus, acting as gatekeepers to contain and resolve infection. Recent studies have highlighted the important roles of macrophages during S. aureus infections, using a wide array of killing mechanisms. In defense, S. aureus has evolved multiple strategies to survive within, manipulate and escape from macrophages, allowing them to not only subvert but also exploit this key element of our immune system. Macrophage-S. aureus interactions are multifaceted and have direct roles in infection outcome. In depth understanding of these host-pathogen interactions may be useful for future therapeutic developments. This review examines macrophage interactions with S. aureus throughout all stages of infection, with special emphasis on mechanisms that determine infection outcome.

scholarly journals Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Kathleen L. McCoy
Keyword(s):  
Pattern Recognition ◽  
Immune Cells ◽  
Innate Immune System ◽  
Cannabinoid Receptors ◽  
Inflammatory Responses ◽  
Endocannabinoid System ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Toll Like Receptor ◽  
Receptor Family

Since the discovery of the endocannabinoid system consisting of cannabinoid receptors, endogenous ligands, and biosynthetic and metabolizing enzymes, interest has been renewed in investigating the promise of cannabinoids as therapeutic agents. Abundant evidence indicates that cannabinoids modulate immune responses. An inflammatory response is triggered when innate immune cells receive a danger signal provided by pathogen- or damage-associated molecular patterns engaging pattern-recognition receptors. Toll-like receptor family members are prominent pattern-recognition receptors expressed on innate immune cells. Cannabinoids suppress Toll-like receptor-mediated inflammatory responses. However, the relationship between the endocannabinoid system and innate immune system may not be one-sided. Innate immune cells express cannabinoid receptors and produce endogenous cannabinoids. Hence, innate immune cells may play a role in regulating endocannabinoid homeostasis, and, in turn, the endocannabinoid system modulates local inflammatory responses. Studies designed to probe the interaction between the innate immune system and the endocannabinoid system may identify new potential molecular targets in developing therapeutic strategies for chronic inflammatory diseases. This review discusses the endocannabinoid system and Toll-like receptor family and evaluates the interaction between them.

scholarly journals Innate Immune Cells in the Esophageal Tumor Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Kele Cui ◽  
Shouxin Hu ◽  
Xinyu Mei ◽  
Min Cheng
Keyword(s):  
Immune Cells ◽  
Molecular Mechanisms ◽  
Survival Rates ◽  
Immune Defense ◽  
Innate Immune ◽  
Esophageal Tumor ◽  
Esophageal Mucosa ◽  
Innate Immune Cells ◽  
Γδt Cells ◽  
Immunological Mechanisms

Esophageal cancer (EC) is one of the most common mucosa-associated tumors, and is characterized by aggressiveness, poor prognosis, and unfavorable patient survival rates. As an organ directly exposed to the risk of foodborne infection, the esophageal mucosa harbors distinct populations of innate immune cells, which play vital roles in both maintenance of esophageal homeostasis and immune defense and surveillance during mucosal anti-infection and anti-tumor responses. In this review, we highlight recent progress in research into innate immune cells in the microenvironment of EC, including lymphatic lineages, such as natural killer and γδT cells, and myeloid lineages, including macrophages, dendritic cells, neutrophils, myeloid-derived suppressor cells, mast cells and eosinophils. Further, putative innate immune cellular and molecular mechanisms involved in tumor occurrence and progression are discussed, to highlight potential directions for the development of new biomarkers and effective intervention targets, which can hopefully be applied in long-term multilevel clinical EC treatment. Fully understanding the innate immunological mechanisms involved in esophageal mucosa carcinogenesis is of great significance for clinical immunotherapy and prognosis prediction for patients with EC.

scholarly journals Neutrophils as regulators of the hematopoietic niche

Blood ◽  
2019 ◽  
Vol 133 (20) ◽  
pp. 2140-2148 ◽  
Author(s):  
Itziar Cossío ◽  
Daniel Lucas ◽  
Andrés Hidalgo
Keyword(s):  
Immune Cells ◽  
Innate Immune System ◽  
Dynamic Structure ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Physiological Demands ◽  
Hematopoietic Niche

Abstract The niche that supports hematopoietic stem and progenitor cells (HSPCs) in the bone marrow is a highly dynamic structure. It maintains core properties of HSPCs in the steady state, and modulates their proliferation and differentiation in response to changing physiological demands or pathological insults. The dynamic and environment-sensing properties of the niche are shared by the innate immune system. Thus, it is not surprising that innate immune cells, including macrophages and neutrophils, are now recognized as important regulators of the hematopoietic niche and, ultimately, of the stem cells from which they derive. This review synthesizes emerging concepts on niche regulation by immune cells, with a particular emphasis on neutrophils. We argue that the unique developmental, circadian, and migratory properties of neutrophils underlie their critical contributions as regulators of the hematopoietic niche.

scholarly journals Microbiome management in the social amoeba Dictyostelium discoideum compared to humans

2019 ◽  
Vol 63 (8-9-10) ◽  
pp. 447-450 ◽  
Author(s):  
Timothy Farinholt ◽  
Christopher Dinh ◽  
Adam Kuspa
Keyword(s):  
Recent Work ◽  
Dictyostelium Discoideum ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Social Amoeba ◽  
The Social ◽  
Physical Barriers ◽  
Social Amoebae

Social amoebae and humans use common strategies to orchestrate their interactions with the bacteria in their respective environments and within their bodies. These strategies include the elimination of bacteria by phagocytosis, the establishment of mutualistic interactions, the elaboration of physical barriers, and the deployment of innate immune cells. Many of the molecular mechanisms that humans and social amoebae employ differ, but there are striking similarities that may inform studies in each organism. In this topical review we highlight the similarities and consider what we might learn by comparing these highly divergent species. We focus on recent work in Dictyostelium discoideum with hopes of stimulating work in this area and with the expectation that new mechanistic details uncovered in social amoebae-bacteria interactions will inform microbiome management in humans.

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