scholarly journals Controlled Human Malaria Infection Induces Long-Term Functional Changes in Monocytes

2020 ◽  
Vol 7 ◽  
Author(s):  
Jona Walk ◽  
Farid Keramati ◽  
L. Charlotte J. de Bree ◽  
Rob J. W. Arts ◽  
Bas Blok ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Oxidized Ldl ◽  
Acute Infection ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Human Malaria ◽  
Trained Immunity ◽  
Controlled Human Malaria Infection

Innate immune memory responses (also termed “trained immunity”) have been described in monocytes after BCG vaccination and after stimulation in vitro with microbial and endogenous ligands such as LPS, β-glucan, oxidized LDL, and monosodium urate crystals. However, whether clinical infections are also capable of inducing a trained immunity phenotype remained uncertain. We evaluated whether Plasmodium falciparum infection can induce innate immune memory by measuring monocyte-derived cytokine production from five volunteers undergoing Controlled Human Malaria Infection. Monocyte responses followed a biphasic pattern: during acute infection, monocytes produced lower amounts of inflammatory cytokines upon secondary stimulation, but 36 days after malaria infection they produced significantly more IL-6 and TNF-α in response to various stimuli. Furthermore, transcriptomic and epigenomic data analysis revealed a clear reprogramming of monocytes at both timepoints, with long-term changes of H3K4me3 at the promoter regions of inflammatory genes that remain present for several weeks after parasite clearance. These findings demonstrate an epigenetic basis of trained immunity induced by human malaria in vivo.

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 Trained Immunity

2020 ◽  
Author(s):  
Helin Tercan ◽  
Niels P. Riksen ◽  
Leo A.B. Joosten ◽  
Mihai G. Netea ◽  
Siroon Bekkering
Keyword(s):  
Immune Cells ◽  
Inflammatory Diseases ◽  
Oxidized Ldl ◽  
Density Lipoprotein ◽  
Innate Immune ◽  
Immune Memory ◽  
Innate Immune Cells ◽  
Antigen Specificity ◽  
Trained Immunity

Adaptive immune responses are characterized by antigen specificity and induction of lifelong immunologic memory. Recently, it has been reported that innate immune cells can also build immune memory characteristics—a process termed trained immunity. Trained immunity describes the persistent hyperresponsive phenotype that innate immune cells can develop after brief stimulation. Pathogenic stimuli such as microorganisms, and also endogenous molecules including uric acid, oxidized LDL (low-density lipoprotein), and catecholamines, are capable of inducing memory in monocytes and macrophages. While trained immunity provides favorable cross-protection in the context of infectious diseases, the heightened immune response can be maladaptive in diseases driven by chronic systemic inflammation, such as atherosclerosis. Trained immunity is maintained by distinct epigenetic and metabolic mechanisms and persists for at least several months in vivo due to reprogramming of myeloid progenitor cells. Additionally, certain nonimmune cells are also found to exhibit trained immunity characteristics. Thus, trained immunity presents an exciting framework to develop new approaches to vaccination and also novel pharmacological targets in the treatment of inflammatory diseases.

scholarly journals Induction of Trained Innate Immunity in Human Monocytes by Bovine Milk and Milk-Derived Immunoglobulin G

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1378 ◽  
Author(s):  
Marloes van Splunter ◽  
Thijs van Osch ◽  
Sylvia Brugman ◽  
Huub Savelkoul ◽  
Leo Joosten ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immunoglobulin G ◽  
Cytokine Production ◽  
Bovine Milk ◽  
Innate Immune ◽  
Immune Memory ◽  
Bovine Lactoferrin ◽  
Human Monocytes ◽  
Trained Immunity

Innate immune memory, also termed “trained immunity” in vertebrates, has been recently described in a large variety of plants and animals. In most cases, trained innate immunity is induced by pathogens or pathogen-associated molecular patterns (PAMPs), and is associated with long-term epigenetic, metabolic, and functional reprogramming. Interestingly, recent findings indicate that food components can mimic PAMPs effects and induce trained immunity. The aim of this study was to investigate whether bovine milk or its components can induce trained immunity in human monocytes. To this aim, monocytes were exposed for 24 h to β-glucan, Toll-like receptor (TLR)-ligands, bovine milk, milk fractions, bovine lactoferrin (bLF), and bovine Immunoglobulin G (bIgG). After washing away the stimulus and a resting period of five days, the cells were re-stimulated with TLR ligands and Tumor necrosis factor (TNF-) and interleukin (IL)-6 production was measured. Training with β-glucan resulted in higher cytokine production after TLR1/2, TLR4, and TLR7/8 stimulation. When monocytes trained with raw milk were re-stimulated with TLR1/2 ligand Pam3CSK4, trained cells produced more IL-6 compared to non-trained cells. Training with bIgG resulted in higher cytokine production after TLR4 and TLR7/8 stimulation. These results show that bovine milk and bIgG can induce trained immunity in human monocytes. This confirms the hypothesis that diet components can influence the long-term responsiveness of the innate immune system.

scholarly journals Trained Immunity and Local Innate Immune Memory in the Lung

Cell ◽  
2018 ◽  
Vol 175 (6) ◽  
pp. 1463-1465 ◽  
Author(s):  
Mihai G. Netea ◽  
Leo A.B. Joosten
Keyword(s):  
Innate Immune ◽  
Immune Memory ◽  
Trained Immunity

scholarly journals Immunoprofiles associated with controlled human malaria infection and naturally acquired immunity identify a shared IgA pre-erythrocytic immunoproteome

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Andrea A. Berry ◽  
Joshua M. Obiero ◽  
Mark A. Travassos ◽  
Amed Ouattara ◽  
Drissa Coulibaly ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Vaccine Development ◽  
Protein Microarray ◽  
Antibody Responses ◽  
Liver Stage ◽  
Human Malaria ◽  
Controlled Human Malaria Infection ◽  
Iga Antibody ◽  
Potential Vaccine ◽  
Antigen Protein

AbstractKnowledge of the Plasmodium falciparum antigens that comprise the human liver stage immunoproteome is important for pre-erythrocytic vaccine development, but, compared with the erythrocytic stage immunoproteome, more challenging to classify. Previous studies of P. falciparum antibody responses report IgG and rarely IgA responses. We assessed IgG and IgA antibody responses in adult sera collected during two controlled human malaria infection (CHMI) studies in malaria-naïve volunteers and in 1- to 6-year-old malaria-exposed Malian children on a 251 P. falciparum antigen protein microarray. IgG profiles in the two CHMI groups were equivalent and differed from Malian children. IgA profiles were robust in the CHMI groups and a subset of Malian children. We describe immunoproteome differences in naïve vs. exposed individuals and report pre-erythrocytic proteins recognized by the immune system. IgA responses detected in this study expand the list of pre-erythrocytic antigens for further characterization as potential vaccine candidates.

scholarly journals Outcomes of controlled human malaria infection after BCG vaccination

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jona Walk ◽  
L. Charlotte J. de Bree ◽  
Wouter Graumans ◽  
Rianne Stoter ◽  
Geert-Jan van Gemert ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Human Malaria ◽  
Bcg Vaccination ◽  
Controlled Human Malaria Infection
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