scholarly journals Crosstalk Between Autophagy and Hypoxia-Inducible Factor-1α in Antifungal Immunity

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2150 ◽  
Author(s):  
Tim Quäschling ◽  
Dirk Friedrich ◽  
George S. Deepe ◽  
Jan Rupp
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Fungal Pathogens ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Hypoxia Inducible Factor ◽  
Canonical Pathway ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Hypoxia Inducible Factor 1Α

Modern medicine is challenged by several potentially severe fungal pathogens such as Aspergillus fumigatus, Candida albicans, or Histoplasma capsulatum. Though not all fungal pathogens have evolved as primary pathogens, opportunistic pathogens can still cause fatal infections in immuno-compromised patients. After infection with these fungi, the ingestion and clearance by innate immune cells is an important part of the host immune response. Innate immune cells utilize two different autophagic pathways, the canonical pathway and the non-canonical pathway, also called microtubule-associated protein 1A/1B-light chain 3 (LC3) -associated pathway (LAP), to clear fungal pathogens from the intracellular environment. The outcome of autophagy-related host immune responses depends on the pathogen and cell type. Therefore, the understanding of underlying molecular mechanisms of autophagy is crucial for the development and improvement of antifungal therapies. One of those molecular mechanisms is the interaction of the transcription-factor hypoxia-inducible factor 1α (HIF-1α) with the autophagic immune response. During this review, we will focus on a comprehensive overview of the role of autophagy and HIF-1α on the outcome of fungal infections.

scholarly journals Helminth Infections: Recognition and Modulation of the Immune Response by Innate Immune Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Claudia Cristina Motran ◽  
Leonardo Silvane ◽  
Laura Silvina Chiapello ◽  
Martin Gustavo Theumer ◽  
Laura Fernanda Ambrosio ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Helminth Infections

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 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 Interfering with MIF-CD74 signalling on macrophages and dendritic cells with a peptide-based approach restores the immune response against metastatic melanoma

2018 ◽  
Author(s):  
Carlos R. Figueiredo ◽  
Ricardo A. Azevedo ◽  
Sasha Mousdell ◽  
Pedro T. Resende-Lara ◽  
Lucy Ireland ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Metastatic Melanoma ◽  
Immune Cells ◽  
Tumour Microenvironment ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Adaptive Immune Cells ◽  
Cancer Immunotherapies

ABSTRACTMounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. Immunotherapies that boost the activity of effector T cells have shown a remarkable success in melanoma treatment. Patients, however, can develop resistance to such therapies by mechanisms that include the establishment of an immune suppressive tumour microenvironment. Understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that the innate immune cells, macrophages and dendritic cells are suppressed in metastatic melanoma. The Ig-CDR-based peptide C36L1 is able to restore macrophages and dendritic cells’ immunogenic functions and to inhibit metastatic growth in vivo. Mechanistically, we found that C36L1 interferes with the MIF-CD74 tumour-innate immune cells immunosuppressive signalling pathway and thereby restores an effective anti-tumour immune response. C36L1 directly binds to CD74 on macrophages and dendritic cells, disturbing CD74 structural dynamics and inhibiting MIF signalling through CD74. Our findings suggest that interfering with MIF-CD74 immunosuppressive signalling in macrophages and dendritic cells using peptide-based immunotherapy can restore the anti-tumour immune response in metastatic melanoma. Our study provides the rationale for further development of peptide-based therapies to restore the anti-tumour immune response.

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 The Role of Syk/CARD9-Coupled C-Type Lectin Receptors in Immunity toMycobacterium tuberculosisInfections

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Mohlopheni Jackson Marakalala ◽  
Lisa M. Graham ◽  
Gordon D. Brown
Keyword(s):  
Immune Response ◽  
Pattern Recognition ◽  
Mycobacterium Tuberculosis ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Lectin Receptors ◽  
Molecular Patterns

There is increasing interest in understanding the mechanisms underlying the interactions that occur betweenMycobacterium tuberculosisand host innate immune cells. These cells express pattern recognition receptors (PRRs) which recognise mycobacterial pathogen-associated molecular patterns (PAMPs) and which can influence the host immune response to the infection. Although many of the PRRs appear to be redundant in the control ofM. tuberculosisinfectionin vivo, recent discoveries have revealed a key, nonredundant, role of the Syk/CARD9 signalling pathway in antimycobacterial immunity. Here we review these discoveries, as well as recent data investigating the role of the Syk/CARD9-coupled PRRs that have been implicated in mycobacterial recognition, including Dectin-1 and Mincle.

scholarly journals Species-Specific Endotoxin Stimulus Determines Toll-Like Receptor 4- and Caspase 11-Mediated Pathway Activation Characteristics

mSystems ◽  
2021 ◽  
Author(s):  
Orna Ernst ◽  
Mohd M. Khan ◽  
Benjamin L. Oyler ◽  
Sung Hwan Yoon ◽  
Jing Sun ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Surface ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Pathway Activation ◽  
Specific Receptors ◽  
Species Specific

Macrophages and monocytes are innate immune cells playing an important role in orchestrating the initial innate immune response to bacterial infection and the tissue damage. This response is facilitated by specific receptors on the cell surface and intracellularly.

Latest Advances in Small Molecule TLR 7/8 Agonist Drug Research

2019 ◽  
Vol 19 (24) ◽  
pp. 2228-2238 ◽  
Author(s):  
David C. McGowan
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Small Molecule ◽  
Immune Cells ◽  
Drug Research ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Small Molecule Activation ◽  
Evolutionarily Conserved ◽  
Recent Developments

Toll-like receptors (TLRs) 7 and 8 play an important role in the activation of innate immune cells in mammals. These evolutionarily conserved receptors serve as important sentinels in response to infection. Activation of TLRs 7 and 8 triggers induction of a Th1 type innate immune response. The emergence of new structural and small molecule information generated in the last decade has contributed enormously to our understanding of this highly sophisticated process of innate immunity signaling. This review will focus on recent developments in the small molecule activation of TLR 7 and 8.

scholarly journals Redox Signaling from Mitochondria: Signal Propagation and Its Targets

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 93 ◽  
Author(s):  
Petr Ježek ◽  
Blanka Holendová ◽  
Lydie Plecitá-Hlavatá
Keyword(s):  
Skeletal Muscle ◽  
Insulin Secretion ◽  
Immune Cells ◽  
Hypoxia Inducible Factor ◽  
Signal Propagation ◽  
Redox Signaling ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Stimulation Of

Progress in mass spectroscopy of posttranslational oxidative modifications has enabled researchers to experimentally verify the concept of redox signaling. We focus here on redox signaling originating from mitochondria under physiological situations, discussing mechanisms of transient redox burst in mitochondria, as well as the possible ways to transfer such redox signals to specific extramitochondrial targets. A role of peroxiredoxins is described which enables redox relay to other targets. Examples of mitochondrial redox signaling are discussed: initiation of hypoxia-inducible factor (HIF) responses; retrograde redox signaling to PGC1α during exercise in skeletal muscle; redox signaling in innate immune cells; redox stimulation of insulin secretion, and other physiological situations.

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