scholarly journals Identification of a prostaglandin E2 receptor that regulates mosquito oenocytoid immune cell function in limiting bacteria and parasite infection

2020 ◽  
Author(s):  
Hyeogsun Kwon ◽  
David R. Hall ◽  
Ryan C. Smith

AbstractLipid-derived signaling molecules known as eicosanoids have integral roles in mediating immune and inflammatory processes across metazoans. This includes the function of prostaglandins and their cognate G protein-coupled receptors (GPCRs) to employ their immunological actions. In insects, prostaglandins have been implicated in the regulation of both cellular and humoral immune responses, yet studies have been limited by the absence of a described prostaglandin receptor. Here, we characterize a prostaglandin E2 receptor (AgPGE2R) in the mosquito Anopheles gambiae and examine its contributions to innate immunity. AgPGE2R expression is most abundant in circulating hemocytes where it is primarily localized to oenocytoid immune cell populations. Through the administration of prostaglandin E2 (PGE2) and AgPGE2R-silencing by RNAi, we demonstrate that PGE2 signaling regulates the expression of a subset of prophenoloxidases (PPOs) and antimicrobial peptides (AMPs). PGE2 priming via the AgPGE2R significantly limited bacterial replication and suppressed Plasmodium oocyst survival. Additional experiments establish that PGE2 priming increases phenoloxidase (PO) activity through the increased expression of PPO1 and PPO3, which significantly influence Plasmodium oocyst survival. We also provide evidence that PGE2 priming is concentration-dependent, where high concentrations of PGE2 promote oenocytoid lysis, negating the protective effects of PGE2 priming on anti-Plasmodium immunity. Taken together, our results characterize the AgPGE2R and the role of prostaglandin signaling on immune cell function, providing new insights into the role of PGE2 on anti-bacterial and anti-Plasmodium immune responses in the mosquito host.

2021 ◽  
Vol 12 ◽  
Author(s):  
Hyeogsun Kwon ◽  
David R. Hall ◽  
Ryan C. Smith

Lipid-derived signaling molecules known as eicosanoids have integral roles in mediating immune and inflammatory processes across metazoans. This includes the function of prostaglandins and their cognate G protein-coupled receptors (GPCRs) to employ their immunological actions. In insects, prostaglandins have been implicated in the regulation of both cellular and humoral immune responses, yet in arthropods of medical importance, studies have been limited. Here, we describe a prostaglandin E2 receptor (AgPGE2R) in the mosquito Anopheles gambiae and demonstrate that its expression is most abundant in oenocytoid immune cell populations. Through the administration of prostaglandin E2 (PGE2) and AgPGE2R-silencing, we demonstrate that prostaglandin E2 signaling regulates a subset of prophenoloxidases (PPOs) and antimicrobial peptides (AMPs) that are strongly expressed in populations of oenocytoids. We demonstrate that PGE2 signaling via the AgPGE2R significantly limits both bacterial replication and Plasmodium oocyst survival. Additional experiments establish that PGE2 treatment increases phenoloxidase (PO) activity through the increased expression of PPO1 and PPO3, genes essential to anti-Plasmodium immune responses that promote oocyst killing. We also provide evidence that the mechanisms of PGE2 signaling are concentration-dependent, where high concentrations of PGE2 promote oenocytoid lysis, negating the protective effects of lower concentrations of PGE2 on anti-Plasmodium immunity. Taken together, our results provide new insights into the role of PGE2 signaling on immune cell function and its contributions to mosquito innate immunity that promote pathogen killing.


Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1280 ◽  
Author(s):  
Rébé ◽  
Ghiringhelli

Immune cells in the tumor microenvironment regulate cancer growth. Thus cancer progression is dependent on the activation or repression of transcription programs involved in the proliferation/activation of lymphoid and myeloid cells. One of the main transcription factors involved in many of these pathways is the signal transducer and activator of transcription 3 (STAT3). In this review we will focus on the role of STAT3 and its regulation, e.g. by phosphorylation or acetylation in immune cells and how it might impact immune cell function and tumor progression. Moreover, we will review the ability of STAT3 to regulate checkpoint inhibitors.


2019 ◽  
Vol 15 (9) ◽  
pp. 546-558 ◽  
Author(s):  
Nicola Wilck ◽  
András Balogh ◽  
Lajos Markó ◽  
Hendrik Bartolomaeus ◽  
Dominik N. Müller

2021 ◽  
pp. ji2001395
Author(s):  
Sannette C. Hall ◽  
Deandra R. Smith ◽  
Shetty Ravi Dyavar ◽  
Todd A. Wyatt ◽  
Derrick R. Samuelson ◽  
...  

Immunology ◽  
2018 ◽  
Vol 154 (3) ◽  
pp. 346-353 ◽  
Author(s):  
Ralf Willebrand ◽  
Markus Kleinewietfeld

Cell Stress ◽  
2021 ◽  
Vol 5 (3) ◽  
pp. 29-32
Author(s):  
Andreas Zimmermann ◽  
Didac Carmona-Gutierrez ◽  
Frank Madeo

The polyamine spermidine is essential for protein translation in eukaryotes, both as a substrate for the hypusination of the translation initiation factor eIF5A as well as general translational fidelity. Dwindling spermidine levels during aging have been implicated in reduced immune cell function through insufficient eIF5A hypusination, which can be restored by external supplementation. Recent findings characterize a group of novel Mendelian disorders linked to EIF5A missense and nonsense variants that cause protein translation defects. In model organisms that recapitulate these mutations, spermidine supplementation was able to alleviate at least some of the concomitant protein translation defects. Here, we discuss the role of spermidine in protein translation and possible therapeutic avenues for translation-associated disorders.


2012 ◽  
Vol 18 (5) ◽  
pp. 745-752 ◽  
Author(s):  
Anna Konermann ◽  
Dirk Stabenow ◽  
Percy A Knolle ◽  
Stefanie AE Held ◽  
James Deschner ◽  
...  

Author(s):  
Mohammad Javad Fattahi ◽  
Mohammad Reza Haghshenas ◽  
Abbas Ghaderi

Abstract: The initiation and progression of bladder cancer (BC), is dependent on its tumor microenvironment (TME). On the other hand, cancer cells shape and train TME to support their development, respond to treatment and migration in an organism. Immune cells exert key roles in the BC microenvironment and have complex interactions with BC cells. These complicated interplays result in metabolic competition in the TME leading to nutrient deprivation, acidosis, hypoxia and metabolite accumulation, which impair immune cell function. Recent studies have demonstrated that immune cells functions are closely correlated with their metabolism. Immunometabolism describes the functional metabolic alterations that take place within immune cells and the role of these cells in directing metabolism and immune response in tissues or diseases such as cancer. Some molecules and their metabolites in the TME including glucose, fatty acids and amino acids can regulate the phenotype, function and metabolism of immune cells. Hence, here we describe some recent advances in immunometabolism and relate them to BC progression. A profound understanding of the metabolic reprogramming of BC cells and immune cells in the TME will offer novel opportunities for targeted therapies in future.


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