scholarly journals Targeting immunometabolism in host-directed therapies to fungal disease

2021 ◽  
Author(s):  
Samuel M Gonçalves ◽  
Anaísa V Ferreira ◽  
Cristina Cunha ◽  
Agostinho Carvalho
Keyword(s):  
Antifungal Activity ◽  
Immune Responses ◽  
Immune Cells ◽  
Metabolic Regulation ◽  
Therapeutic Potential ◽  
Fungal Infections ◽  
Cellular Metabolism ◽  
Therapeutic Approaches ◽  
Effector Functions ◽  
Host Fungus

Abstract Fungal infections affect over a billion people and are responsible for more than 1.5 million deaths each year. Despite progress in diagnostic and therapeutic approaches, the management of severe fungal infections remains a challenge. Recently, the reprogramming of cellular metabolism has emerged as a central mechanism through which the effector functions of immune cells are supported to promote antifungal activity. An improved understanding of the immunometabolic signatures that orchestrate antifungal immunity, together with the dissection of the mechanisms that underlie heterogeneity in individual immune responses, may therefore unveil new targets amenable to adjunctive host-directed therapies. In this review, we highlight recent advances in the metabolic regulation of host-fungus interactions and antifungal immune responses, and outline targetable pathways and mechanisms with promising therapeutic potential.

scholarly journals Lactate-Dependent Regulation of Immune Responses by Dendritic Cells and Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Indumathi Manoharan ◽  
Puttur D. Prasad ◽  
Muthusamy Thangaraju ◽  
Santhakumar Manicassamy
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Adaptive Immune Responses ◽  
Effector Functions ◽  
Tissue Microenvironment ◽  
Adaptive Immune ◽  
Pathological Conditions ◽  
Recent Advances ◽  
Adaptive Immune Cells

For decades, lactate has been considered an innocuous bystander metabolite of cellular metabolism. However, emerging studies show that lactate acts as a complex immunomodulatory molecule that controls innate and adaptive immune cells’ effector functions. Thus, recent advances point to lactate as an essential and novel signaling molecule that shapes innate and adaptive immune responses in the intestine and systemic sites. Here, we review these recent advances in the context of the pleiotropic effects of lactate in regulating diverse functions of immune cells in the tissue microenvironment and under pathological conditions.

Metabolic regulation of natural killer cells

2015 ◽  
Vol 43 (4) ◽  
pp. 758-762 ◽  
Author(s):  
David K. Finlay
Keyword(s):  
Immune Responses ◽  
Nk Cells ◽  
Natural Killer ◽  
Metabolic Regulation ◽  
Immune Cell ◽  
Nk Cell ◽  
Cellular Metabolism ◽  
T Cell Subsets ◽  
Immune Cell Subsets ◽  
Mtor Complex 1

Natural killer (NK) cells have key roles in anti-viral and anti-tumour immune responses. Recent research demonstrates that cellular metabolism is an important determinant for the function of pro-inflammatory immune cells, including activated NK cells. The mammalian target of rapamcyin (mTOR) complex 1 (mTORC1) has been identified as a key metabolic regulator that promotes glycolytic metabolism in multiple immune cell subsets. Glycolysis is integrally linked to pro-inflammatory immune responses such that activated NK cells and effector T-cell subsets are reliant on sufficient glucose availability for maximal effector function. This article will discuss the regulation of cellular metabolism in NK cells as compared with that of T lymphocytes and discuss the implications for NK cell responses to viral infection and cancer.

scholarly journals A Nomogram Integrating Ferroptosis- and Immune-Related Biomarkers for Prediction of Overall Survival in Lung Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengyu Chai ◽  
Xiuchun Li ◽  
Yaxin Zhang ◽  
Yemeng Tang ◽  
Pingping Shu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Responses ◽  
Lung Adenocarcinoma ◽  
Tumor Immunity ◽  
Immune Cells ◽  
Cox Regression ◽  
Therapeutic Potential ◽  
Clinical Staging ◽  
Risk Scores ◽  
Immune Related Genes

Ferroptosis plays a dual role in cancer, which is known to be affected to antitumor immune responses. However, the association between ferroptosis and antitumor immune responses is uncertain in lung adenocarcinoma (LUAD). In this work, 38 ferroptosis-related genes (FRGs) and 429 immune-related genes (IRGs) were identified as being differentially expressed between tumor and normal samples. Two risk score formulas consisting of seven FRGs and four IRGs, respectively, were developed by Lasso-penalized Cox regression and verified in the GSE13213 dataset. The CIBERSORT algorithm was used to estimate the relative abundance of immune cells in tumors. The correlation between FRGs and immune cells was evaluated using the TIMER database. The results indicated that the development of ferroptosis was synergistic with that of anti-tumor immunity in LUAD. The concordance index and calibration curves showed that the performance of a nomogram that combines clinical staging and risk scores is superior to that of models using a single prognostic factor. In conclusion, ferroptosis might be synergistic with anti-tumor immunity in LUAD. The combined nomogram could reliably predict the probability of overall survival of LUAD patients. These findings may be useful for future investigation of prognostic value and therapeutic potential related to ferroptosis and tumor immunity in LUAD.

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 Dendritic Cells The Tumor Microenvironment and the Challenges for an Effective Antitumor Vaccination

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Fabian Benencia ◽  
Leslee Sprague ◽  
John McGinty ◽  
Michelle Pate ◽  
Maria Muccioli
Keyword(s):  
Clinical Trials ◽  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Immune Cells ◽  
Therapeutic Potential ◽  
Human Cancer ◽  
Dc Vaccines ◽  
Tumor Clearance ◽  
Antigen Presenting

Many clinical trials have been carried out or are in progress to assess the therapeutic potential of dendritic-cell- (DC-) based vaccines on cancer patients, and recently the first DC-based vaccine for human cancer was approved by the FDA. Herewith, we describe the general characteristics of DCs and different strategies to generate effective antitumor DC vaccines. In recent years, the relevance of the tumor microenvironment in the progression of cancer has been highlighted. It has been shown that the tumor microenvironment is capable of inactivating various components of the immune system responsible for tumor clearance. In particular, the effect of the tumor microenvironment on antigen-presenting cells, such as DCs, does not only render these immune cells unable to induce specific immune responses, but also turns them into promoters of tumor growth. We also describe strategies likely to increase the efficacy of DC vaccines by reprogramming the immunosuppressive nature of the tumor microenvironment.

scholarly journals Lipid Metabolism and Cancer Immunotherapy: Immunosuppressive Myeloid Cells at the Crossroad

2020 ◽  
Vol 21 (16) ◽  
pp. 5845
Author(s):  
Augusto Bleve ◽  
Barbara Durante ◽  
Antonio Sica ◽  
Francesca Maria Consonni
Keyword(s):  
Lipid Metabolism ◽  
Immune Responses ◽  
Cancer Progression ◽  
Immune Cells ◽  
Therapeutic Potential ◽  
Myeloid Cell ◽  
Major Influence ◽  
Nutrient Competition ◽  
Adaptive Immune Cells ◽  
Inflammatory State

Cancer progression generates a chronic inflammatory state that dramatically influences hematopoiesis, originating different subsets of immune cells that can exert pro- or anti-tumor roles. Commitment towards one of these opposing phenotypes is driven by inflammatory and metabolic stimuli derived from the tumor-microenvironment (TME). Current immunotherapy protocols are based on the reprogramming of both specific and innate immune responses, in order to boost the intrinsic anti-tumoral activity of both compartments. Growing pre-clinical and clinical evidence highlights the key role of metabolism as a major influence on both immune and clinical responses of cancer patients. Indeed, nutrient competition (i.e., amino acids, glucose, fatty acids) between proliferating cancer cells and immune cells, together with inflammatory mediators, drastically affect the functionality of innate and adaptive immune cells, as well as their functional cross-talk. This review discusses new advances on the complex interplay between cancer-related inflammation, myeloid cell differentiation and lipid metabolism, highlighting the therapeutic potential of metabolic interventions as modulators of anticancer immune responses and catalysts of anticancer immunotherapy.

scholarly journals NF-κB and Its Role in Checkpoint Control

2020 ◽  
Vol 21 (11) ◽  
pp. 3949 ◽  
Author(s):  
Annika C. Betzler ◽  
Marie-Nicole Theodoraki ◽  
Patrick J. Schuler ◽  
Johannes Döscher ◽  
Simon Laban ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Tumor Cells ◽  
Immune Checkpoint ◽  
Therapeutic Potential ◽  
Nuclear Factor Κb ◽  
Immune Checkpoint Blockade ◽  
Nuclear Factor ◽  
Checkpoint Control ◽  
Therapeutic Approaches

Nuclear factor-κB (NF-κB) has been described as one of the most important molecules linking inflammation to cancer. More recently, it has become clear that NF-κB is also involved in the regulation of immune checkpoint expression. Therapeutic approaches targeting immune checkpoint molecules, enabling the immune system to initiate immune responses against tumor cells, constitute a key breakthrough in cancer treatment. This review discusses recent evidence for an association of NF-κB and immune checkpoint expression and examines the therapeutic potential of inhibitors targeting either NF-κB directly or molecules involved in NF-κB regulation in combination with immune checkpoint blockade.

scholarly journals Chitin, Chitinase Responses, and Invasive Fungal Infections

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Karina Vega ◽  
Markus Kalkum
Keyword(s):  
Immune Responses ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Therapeutic Approaches ◽  
Human Immune System ◽  
Cell Wall Component ◽  
Diagnostic Assays ◽  
Host Immune Responses ◽  
Human Immune ◽  
Novel Therapeutic

The human immune system is capable of recognizing and degrading chitin, an important cell wall component of pathogenic fungi. In the context of host-immune responses to fungal infections, herein we review the particular contributions and interplay of fungus and chitin recognition, and chitin-degrading enzymes, known as chitinases. The mechanisms of host chitinase responses may have implications for diagnostic assays as well as novel therapeutic approaches for patients that are at risk of contracting fatal fungal infections.

Should we Try to Alleviate Immunosenescence and Inflammaging - Why, How and to What Extent?

2019 ◽  
Vol 25 (39) ◽  
pp. 4154-4162 ◽  
Author(s):  
Jacek M. Witkowski ◽  
Ewa Bryl ◽  
Tamas Fulop
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Immune Cells ◽  
Malignant Neoplasm ◽  
Human Beings ◽  
Therapeutic Approaches ◽  
Human Immune System ◽  
Immune Systems ◽  
Human Immune

With advancing age, immune responses of human beings to external pathogens, i.e., bacteria, viruses, fungi and parasites, and to internal pathogens - malignant neoplasm cells - become less effective. Two major features in the process of aging of the human immune system are immunosenescence and inflammaging. The immune systems of our predecessors co-evolved with pathogens, which led to the occurrence of effective immunity. However, the otherwise beneficial activity may pose problems to the organism of the host and so it has builtin brakes (regulatory immune cells) and - with age - it undergoes adaptations and modifications, examples of which are the mentioned inflammaging and immunosenescence. Here we describe the mechanisms that first created our immune systems, then the consequences of their changes associated with aging, and the mechanisms of inflammaging and immunosenescence. Finally, we discuss to what extent both processes are detrimental and to what extent they might be beneficial and propose some therapeutic approaches for their wise control.

Therapeutic Potential of Phytomedicines and Novel Polymeric Strategies for Significant Management of Candidiasis

2018 ◽  
Vol 24 (16) ◽  
pp. 1748-1765 ◽  
Author(s):  
Surbhi Rohilla ◽  
D.C. Bhatt ◽  
Aditi Gupta
Keyword(s):  
Therapeutic Potential ◽  
Fungal Infections ◽  
Fungal Species ◽  
Herbal Remedies ◽  
Therapeutic Approaches ◽  
Synthetic Drugs ◽  
Polymeric Drug Delivery ◽  
Polymeric Drug ◽  
Polymeric Drug Delivery Systems

Background: Candidiasis is one of the most common opportunistic fungal infections caused by genus Candida. The genus is composed of around 200 species. The most virulent among all are, Candida albicans followed by various nonalbicans species. Despite various treatments available, the incidence of severe systemic fungal infections is increasing, and with it the related morbidity and mortality, in relation to the misuse of antimicrobials and the emergence of drug-resistant fungal species. Therefore, various novel therapeutic approaches need to be developed and explored to overcome these limitations and effective management of candidiasis. Objective: In this review, we focused on natural herbal remedies and significance of novel formulation approaches for the treatment of candidiasis. Conclusion: The reported studies suggested the promising role of phytomedicines and novel polymeric drug delivery systems in therapeutic management of candidiasis. Phytomedicines are effective substitutes of synthetic drugs as they are inexpensive with lesser number of side effects. Various novel particulate approaches can be successfully used to reduce fungal burden at the target site.

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