scholarly journals Salmonella Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense

2021 ◽  
Vol 17 (9) ◽  
pp. e1009943
Author(s):  
Saray Gutiérrez ◽  
Julia Fischer ◽  
Raja Ganesan ◽  
Nina Judith Hos ◽  
Gökhan Cildir ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Glycolytic Enzyme ◽  
Metabolic Adaptation ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Serovar Typhimurium ◽  
Extracellular Stimuli ◽  
Molecular Patterns ◽  
Aldolase A

Regulation of cellular metabolism is now recognized as a crucial mechanism for the activation of innate and adaptive immune cells upon diverse extracellular stimuli. Macrophages, for instance, increase glycolysis upon stimulation with pathogen-associated molecular patterns (PAMPs). Conceivably, pathogens also counteract these metabolic changes for their own survival in the host. Despite this dynamic interplay in host-pathogen interactions, the role of immunometabolism in the context of intracellular bacterial infections is still unclear. Here, employing unbiased metabolomic and transcriptomic approaches, we investigated the role of metabolic adaptations of macrophages upon Salmonella enterica serovar Typhimurium (S. Typhimurium) infections. Importantly, our results suggest that S. Typhimurium abrogates glycolysis and its modulators such as insulin-signaling to impair macrophage defense. Mechanistically, glycolysis facilitates glycolytic enzyme aldolase A mediated v-ATPase assembly and the acidification of phagosomes which is critical for lysosomal degradation. Thus, impairment in the glycolytic machinery eventually leads to decreased bacterial clearance and antigen presentation in murine macrophages (BMDM). Collectively, our results highlight a vital molecular link between metabolic adaptation and phagosome maturation in macrophages, which is targeted by S. Typhimurium to evade cell-autonomous defense.

scholarly journals S. Typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense

2021 ◽  
Author(s):  
Saray Gutiérrez ◽  
Julia Fischer ◽  
Raja Ganesan ◽  
Gökhan Cildir ◽  
Martina Wolke ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Glycolytic Enzyme ◽  
Metabolic Adaptation ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Serovar Typhimurium ◽  
Extracellular Stimuli ◽  
Molecular Patterns ◽  
Aldolase A

AbstractRegulation of the cellular metabolism is now recognized as a crucial mechanism for the homeostasis of innate and adaptive immune cells upon diverse extracellular stimuli. Macrophages, for instance, increase glycolysis upon stimulation with pathogen-associated molecular patterns (PAMPs). Conceivably, pathogens also counteract these metabolic changes for their own survival in the host. However, despite this dynamic interplay in host-pathogen interactions, the role of immunometabolism in the context of intracellular bacterial infections is still unclear. Here, employing unbiased metabolomic and transcriptomic approaches, we investigated the role of metabolic adaptations of macrophages upon Salmonella enterica serovar Typhimurium (S. Typhimurium) infections. Importantly, our results suggested that S. Typhimurium abrogates glycolysis and its modulators such as insulin-signaling to impair macrophage defense. Mechanistically, glycolytic enzyme aldolase A is critical for v-ATPase assembly and the acidification of phagosomes upon S. Typhimurium infection, and impairment in the glycolytic machinery eventually leads to decreased bacterial clearance and antigen presentation in macrophages. Collectively, our results highlight a vital molecular link between metabolic adaptation and phagosome maturation in macrophages, which is targeted by S. Typhimurium to evade cell-autonomous defense.

scholarly journals Human Mucosal Mast Cells Capture HIV-1 and Mediate Viraltrans-Infection of CD4+T Cells

2015 ◽  
Vol 90 (6) ◽  
pp. 2928-2937 ◽  
Author(s):  
Ai-Ping Jiang ◽  
Jin-Feng Jiang ◽  
Ji-Fu Wei ◽  
Ming-Gao Guo ◽  
Yan Qin ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cells ◽  
Cell Surface ◽  
Bacterial Infections ◽  
Mucosal Mast Cells ◽  
Mucosal Tissues ◽  
Viral Particles ◽  
Molecular Patterns ◽  
Hiv 1

ABSTRACTThe gastrointestinal mucosa is the primary site where human immunodeficiency virus type 1 (HIV-1) invades, amplifies, and becomes persistently established, and cell-to-cell transmission of HIV-1 plays a pivotal role in mucosal viral dissemination. Mast cells are widely distributed in the gastrointestinal tract and are early targets for invasive pathogens, and they have been shown to have increased density in the genital mucosa in HIV-infected women. Intestinal mast cells express numerous pathogen-associated molecular patterns (PAMPs) and have been shown to combat various viral, parasitic, and bacterial infections. However, the role of mast cells in HIV-1 infection is poorly defined. In this study, we investigated their potential contributions to HIV-1 transmission. Mast cells isolated from gut mucosal tissues were found to express a variety of HIV-1 attachment factors (HAFs), such as DC-SIGN, heparan sulfate proteoglycan (HSPG), and α4β7 integrin, which mediate capture of HIV-1 on the cell surface. Intriguingly, following coculture with CD4+T cells, mast cell surface-bound viruses were efficiently transferred to target T cells. Prior blocking with anti-HAF antibody or mannan before coculture impaired viraltrans-infection. Cell-cell conjunctions formed between mast cells and T cells, to which viral particles were recruited, and these were required for efficient cell-to-cell HIV-1 transmission. Our results reveal a potential function of gut mucosal mast cells in HIV-1 dissemination in tissues. Strategies aimed at preventing viral capture and transfer mediated by mast cells could be beneficial in combating primary HIV-1 infection.IMPORTANCEIn this study, we demonstrate the role of human mast cells isolated from mucosal tissues in mediating HIV-1trans-infection of CD4+T cells. This finding facilitates our understanding of HIV-1 mucosal infection and will benefit the development of strategies to combat primary HIV-1 dissemination.

scholarly journals Tuning cancer fate: the unremitting role of host immunity

Open Biology ◽  
2017 ◽  
Vol 7 (4) ◽  
pp. 170006 ◽  
Author(s):  
B. Calì ◽  
B. Molon ◽  
A. Viola
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Tumour Progression ◽  
Host Immunity ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Immune Mediated ◽  
Immune Cell Subsets ◽  
Therapeutic Protocols

Host immunity plays a central and complex role in dictating tumour progression. Solid tumours are commonly infiltrated by a large number of immune cells that dynamically interact with the surrounding microenvironment. At first, innate and adaptive immune cells successfully cooperate to eradicate microcolonies of transformed cells. Concomitantly, surviving tumour clones start to proliferate and harness immune responses by specifically hijacking anti-tumour effector mechanisms and fostering the accumulation of immunosuppressive immune cell subsets at the tumour site. This pliable interplay between immune and malignant cells is a relentless process that has been concisely organized in three different phases: elimination, equilibrium and escape. In this review, we aim to depict the distinct immune cell subsets and immune-mediated responses characterizing the tumour landscape throughout the three interconnected phases. Importantly, the identification of key immune players and molecules involved in the dynamic crosstalk between tumour and immune system has been crucial for the introduction of reliable prognostic factors and effective therapeutic protocols against cancers.

scholarly journals The Hygiene Hypothesis and New Perspectives—Current Challenges Meeting an Old Postulate

2021 ◽  
Vol 12 ◽  
Author(s):  
Holger Garn ◽  
Daniel Piotr Potaczek ◽  
Petra Ina Pfefferle
Keyword(s):  
Immune Cells ◽  
Hygiene Hypothesis ◽  
Fine Tuning ◽  
Global Changes ◽  
Industrialized Countries ◽  
New Developments ◽  
Asthma Phenotypes ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

During its 30 years history, the Hygiene Hypothesis has shown itself to be adaptable whenever it has been challenged by new scientific developments and this is a still a continuously ongoing process. In this regard, the mini review aims to discuss some selected new developments in relation to their impact on further fine-tuning and expansion of the Hygiene Hypothesis. This will include the role of recently discovered classes of innate and adaptive immune cells that challenges the old Th1/Th2 paradigm, the applicability of the Hygiene Hypothesis to newly identified allergy/asthma phenotypes with diverse underlying pathomechanistic endotypes, and the increasing knowledge derived from epigenetic studies that leads to better understanding of mechanisms involved in the translation of environmental impacts on biological systems. Further, we discuss in brief the expansion of the Hygiene Hypothesis to other disease areas like psychiatric disorders and cancer and conclude that the continuously developing Hygiene Hypothesis may provide a more generalized explanation for health burden in highly industrialized countries also relation to global changes.

scholarly journals Regulation of Blood and Lymphatic Vessels by Immune Cells in Tumors and Metastasis

2019 ◽  
Vol 81 (1) ◽  
pp. 535-560 ◽  
Author(s):  
Massimiliano Mazzone ◽  
Gabriele Bergers
Keyword(s):  
Immune Cells ◽  
Lymphatic Vessels ◽  
Tumor Vasculature ◽  
Therapeutic Approaches ◽  
Cancer Hallmarks ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Vessel Growth ◽  
Lymphatic Vasculature

Research over the last decades has provided strong evidence for the pivotal role of the tumor-associated blood and lymphatic vasculature in supporting immunoevasion and in subverting T cell–mediated immunosurveillance. Conversely, tumor blood and lymphatic vessel growth is in part regulated by the immune system, with infiltrating innate as well as adaptive immune cells providing both immunosuppressive and various angiogenic signals. Thus, tumor angiogenesis and escape of immunosurveillance are two cancer hallmarks that are tightly linked and interregulated by cell constituents from compartments secreting both chemokines and cytokines. In this review, we discuss the implication and regulation of innate and adaptive immune cells in regulating blood and lymphatic angiogenesis in tumor progression and metastases. Moreover, we also highlight novel therapeutic approaches that target the tumor vasculature as well as the immune compartment to sustain and improve therapeutic efficacy in cancer.

In vitro immunogenicity prediction: bridging between innate and adaptive immunity

Bioanalysis ◽  
2021 ◽  
Author(s):  
Sivan Cohen ◽  
Shan Chung
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
In Vitro Assays ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Clinical Consequences ◽  
Immune Cell Response ◽  
Adaptive Immune Systems

Development of antidrug antibodies (ADAs) is an undesirable potential outcome of administration of biotherapeutics and involves the innate and adaptive immune systems. ADAs can have detrimental clinical consequences: they can reduce biotherapeutic efficacy or produce adverse events. Because animal models are considered poor predictors of immunogenicity in humans, in vitro assays with human innate and adaptive immune cells are commonly used alternatives that can reveal cell-mediated unwanted immune responses. Multiple methods have been developed to assess the immune cell response following exposure to biotherapeutics and estimate the potential immunogenicity of biotherapeutics. This review highlights the role of innate and adaptive immune cells as the drivers of immunogenicity and summarizes the use of these cells in assays to predict clinical ADA.

scholarly journals Inflammation and Immune Response in COPD: Where Do We Stand?

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Nikoletta Rovina ◽  
Antonia Koutsoukou ◽  
Nikolaos G. Koulouris
Keyword(s):  
Immune Responses ◽  
Bacterial Infections ◽  
Severe Disease ◽  
Critical Role ◽  
Specific Pattern ◽  
Innate Immune ◽  
Danger Signal ◽  
Cd4 Cells ◽  
Adaptive Immune ◽  
Molecular Patterns

Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD. Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD. Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs) to release “danger signal”. These signals act as ligands to Toll-like receptors (TLRs), triggering the production of cytokines and inducing innate inflammation. In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells. Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs). Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD. This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD.

Learning the Roles of the Hepatic Adaptive Immune System in Hepatocellular Carcinoma—Nature's Guide for Successful Cancer Immunotherapy

2017 ◽  
Vol 37 (03) ◽  
pp. 210-218 ◽  
Author(s):  
Mathias Heikenwälder ◽  
Eli Pikarsky
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System ◽  
Immune Cells ◽  
Protective Immunity ◽  
Adaptive Immune System ◽  
Hepatic Parenchyma ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Pathophysiological Role

AbstractThe different roles of the adaptive immune system in cancer are beginning to unfold. The dramatic responses to immune check point drugs in some tumors generated an accelerated need for understanding the complex set of interactions between tumor and immune cells. In view of the major pathophysiological role of immune cells in hepatocellular carcinoma, it is not surprising that malignant hepatocytes interact extensively with adaptive immune cells, resulting in both protumor immunopathology and antitumor protective immunity. Identifying potential responders to drugs that target the adaptive immune system, monitoring their immune response to the tumor, and devising the best treatment combinations depends on understanding the complex set of interactions taking place within the tumor and in the adjacent hepatic parenchyma.

scholarly journals Allergen-associated molecular patterns: a new trend in modern allergology

2019 ◽  
Vol 18 (1) ◽  
pp. 76-83
Author(s):  
V. S. Sviridova ◽  
P. Yu. Isaev ◽  
V. V. Klimov ◽  
M. I. Romanova ◽  
N. S. Koshkarova
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Adaptive Immune System ◽  
Conserved Motifs ◽  
Immune Mechanisms ◽  
Adaptive Immune ◽  
Molecular Patterns

Over the last decade the role of innate immunity has been known to be crucial for the activation of adaptive immune system. The main triggers that upregulate reactions of innate immunity are small exogenous molecules with conserved motifs, molecular patterns. The article discusses a variety of possible roles of molecular patterns in the immune mechanisms, including the participation of Allergen Associated Molecular Patterns (AAMPs) in allergic processes.

scholarly journals The Immune Regulatory Role of Protein Kinase CK2 and Its Implications for Treatment of Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1932
Author(s):  
Huixian Hong ◽  
Etty N. Benveniste
Keyword(s):  
T Cells ◽  
Protein Kinase ◽  
Immune Cells ◽  
Protein Kinase Ck2 ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Kinase Ck2

Protein Kinase CK2, a constitutively active serine/threonine kinase, fulfills its functions via phosphorylating hundreds of proteins in nearly all cells. It regulates a variety of cellular signaling pathways and contributes to cell survival, proliferation and inflammation. CK2 has been implicated in the pathogenesis of hematologic and solid cancers. Recent data have documented that CK2 has unique functions in both innate and adaptive immune cells. In this article, we review aspects of CK2 biology, functions of the major innate and adaptive immune cells, and how CK2 regulates the function of immune cells. Finally, we provide perspectives on how CK2 effects in immune cells, particularly T-cells, may impact the treatment of cancers via targeting CK2.

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