Double peroxidase and histone acetyltransferase AgTip60 maintain innate immune memory in primed mosquitoes

2021 ◽  
Vol 118 (44) ◽  
pp. e2114242118
Author(s):  
Fabio M. Gomes ◽  
Miles D. W. Tyner ◽  
Ana Beatriz F. Barletta ◽  
Banhisikha Saha ◽  
Lampouguin Yenkoidiok-Douti ◽  
...  
Keyword(s):  
Cellular Immunity ◽  
Messenger Rna ◽  
Histone Acetyltransferase ◽  
Direct Evidence ◽  
Fat Body ◽  
Immune Surveillance ◽  
Innate Immune ◽  
Immune Memory ◽  
Immune Priming ◽  
Sustained Increase

Immune priming in Anopheles gambiae is mediated by the systemic release of a hemocyte differentiation factor (HDF), a complex of lipoxin A4 bound to Evokin, a lipid carrier. HDF increases the proportion of circulating granulocytes and enhances mosquito cellular immunity. Here, we show that Evokin is present in hemocytes and fat-body cells, and messenger RNA (mRNA) expression increases significantly after immune priming. The double peroxidase (DBLOX) enzyme, present in insects but not in vertebrates, is essential for HDF synthesis. DBLOX is highly expressed in oenocytes in the fat-body tissue, and these cells increase in number in primed mosquitoes. We provide direct evidence that the histone acetyltransferase AgTip60 (AGAP001539) is also essential for a sustained increase in oenocyte numbers, HDF synthesis, and immune priming. We propose that oenocytes may function as a population of cells that are reprogrammed, and orchestrate and maintain a broad, systemic, and long-lasting state of enhanced immune surveillance in primed mosquitoes.

scholarly journals “Proliferation of DBLOX Peroxidase-Expressing Oenocytes Maintains Innate Immune Memory in Primed Mosquitoes”

2020 ◽  
Author(s):  
Fabio M. Gomes ◽  
Miles D.W. Tyner ◽  
Ana Beatriz F. Barletta ◽  
Lampougin Yenkoidiok-Douti ◽  
Gaspar E. Canepa ◽  
...  
Keyword(s):  
Anopheles Gambiae ◽  
Cellular Immunity ◽  
Histone Acetyltransferase ◽  
Direct Evidence ◽  
Fat Body ◽  
Immune Surveillance ◽  
Innate Immune ◽  
Body Tissue ◽  
Immune Memory ◽  
Immune Priming

AbstractImmune priming in Anopheles gambiae mosquitoes following infection with Plasmodium parasites is mediated by the systemic release of a hemocyte differentiation factor (HDF), a complex of lipoxin A4 bound to Evokin, a lipid carrier. HDF increases the proportion of circulating granulocytes and enhances mosquito cellular immunity. We found that Evokin is constitutively produced by hemocytes and fat-body cells, but expression increases in response to infection. Insects synthesize lipoxins, but lack lipoxygenases. Here, we show that the Double Peroxidase (DBLOX) enzyme, present in insects but not in vertebrates, is essential for HDF synthesis. DBLOX is highly expressed in oenocytes in the fat body tissue, and these cells proliferate in response to Plasmodium challenge. We provide direct evidence that modifications mediated by the histone acetyltransferase AgTip60 (AGAP01539) are essential for sustained oenocyte proliferation, HDF synthesis and immune priming. We propose that oenocytes function as a population of “memory” cells that continuously release lipoxin to orchestrate and maintain a broad, systemic and long-lasting state of enhanced immune surveillance.

scholarly journals Specific immune priming in the invasive ctenophore Mnemiopsis leidyi

2013 ◽  
Vol 9 (6) ◽  
pp. 20130864 ◽  
Author(s):  
Sören Bolte ◽  
Olivia Roth ◽  
Eva E. R. Philipp ◽  
Julia Saphörster ◽  
Philip Rosenstiel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Innate Immune ◽  
Adaptive Plasticity ◽  
Immune Memory ◽  
Mnemiopsis Leidyi ◽  
Immune Gene ◽  
Immune Priming ◽  
Effector Genes ◽  
Animal Phyla ◽  
Bacterial Treatment

Specific immune priming enables an induced immune response upon repeated pathogen encounter. As a functional analogue to vertebrate immune memory, such adaptive plasticity has been described, for instance, in insects and crustaceans. However, towards the base of the metazoan tree our knowledge about the existence of specific immune priming becomes scattered. Here, we exposed the invasive ctenophore Mnemiopsis leidyi repeatedly to two different bacterial epitopes (Gram-positive or -negative) and measured gene expression. Ctenophores experienced either the same bacterial epitope twice (homologous treatments) or different bacterial epitopes (heterologous treatments). Our results demonstrate that immune gene expression depends on earlier bacterial exposure. We detected significantly different expression upon heterologous compared with homologous bacterial treatment at three immune activator and effector genes. This is the first experimental evidence for specific immune priming in Ctenophora and generally in non-bilaterian animals, hereby adding to our growing notion of plasticity in innate immune systems across all animal phyla.

Innate Immune Surveillance in the Central Nervous System Following Legionella pneumophila Infection

2018 ◽  
Vol 16 (10) ◽  
pp. 1080-1089 ◽  
Author(s):  
Pasqualina Lagana ◽  
Luca Soraci ◽  
Maria Elsa Gambuzza ◽  
Giuseppe Mancuso ◽  
Santi Antonino Delia
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Legionella Pneumophila ◽  
Immune Surveillance ◽  
Innate Immune ◽  
The Central Nervous System

Innate immune memory mediates increased susceptibility to Alzheimeŕs disease-like pathology in sepsis surviving mice

2021 ◽  
Author(s):  
Virginia L. De Sousa ◽  
Suzana B. Araújo ◽  
Leticia M. Antonio ◽  
Mariana Silva-Queiroz ◽  
Lilian C. Colodeti ◽  
...  
Keyword(s):  
Innate Immune ◽  
Immune Memory ◽  
Alzheimers Disease ◽  
Increased Susceptibility

scholarly journals The Role of Cell Metabolism in Innate Immune Memory

2020 ◽  
pp. 1-9
Author(s):  
Anaisa Valido Ferreira ◽  
Jorge Domiguéz-Andrés ◽  
Mihai Gheorghe Netea
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Trained Immunity ◽  
Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

scholarly journals The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory

2021 ◽  
Vol 22 (5) ◽  
pp. 2578
Author(s):  
Trim Lajqi ◽  
Christian Marx ◽  
Hannes Hudalla ◽  
Fabienne Haas ◽  
Silke Große ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Immune Tolerance ◽  
Immune Cells ◽  
Low Dose ◽  
Innate Immune ◽  
Immune Memory ◽  
Innate Immune Cells ◽  
Atp Production ◽  
Dose Dependent

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.

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