Candida albicans Infection Affords Protection against Reinfection via Functional Reprogramming of Monocytes

By J. Quintin, Sadia Saeed, J. Martens, E. Giamarellos‐Bourboulis, D. Ifrim, C. Logie, L. Jacobs, Trees Jansen, B. Kullberg, C. Wijmenga and 5 more. Cell Host and Microbe, 2012

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SUMMARY Immunological memory in vertebrates is often exclusively attributed to T and B cell function. Recently it was proposed that the enhanced and sustained innate immune responses following initial infectious exposure may also afford protection against reinfection. Testing this concept of “trained immunity,” we show that mice lacking functional T and B lymphocytes are protected against reinfection with Candida albicans in a monocyte-dependent manner. C. albicans and fungal cell wall β-glucans induced functional reprogramming of monocytes, leading to enhanced cytokine production in vivo and in vitro. The training required the β-glucan receptor dectin-1 and the noncanonical Raf-1 pathway. Monocyte training by β-glucans was associated with stable changes in histone trimethylation at H3K4, which suggests the involvement of epigenetic mechanisms in this phenomenon. The functional reprogramming of monocytes, reminiscent of similar NK cell properties, supports the concept of “trained immunity” and may be employed for the design of improved vaccination strategies.

Subfields: Immunology, Obstetrics and Gynecology

View Paper: https://www.semanticscholar.org/paper/c92b628ae114e5ac9da43e6e93993dea064c34e0

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In Immunology

Citations in the corpus

Immune Dysfunction as a Cause and Consequence of Malnutrition (2016, background): “tuberculosis compared to unprimed cells [75].”
Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity (2016, methodology): “Cells were washed twice in PBS. Training of adherent monocytes was performed as previously described (Quintin et al., 2012); see also below.”
β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance (2016, positive): “Depending on the modification, 2%–31% of marked regions showed dynamics during differentiation or LPS or BG exposure, with H3K27ac at promoters and enhancers being the most dynamic mark in number and range (Figure S1; Table S1).”
From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation (2014, background): “Innate memory plays an important defensive role in organisms lacking adaptive immunity, such as plants and invertebrates, but it is evident also in vertebrates lacking functional T and B lymphocytes (220).”
Metabolic Induction of Trained Immunity through the Mevalonate Pathway. (2018, positive): “Indeed, mevalonate induced an enrichment of H3K4me3 on the promoters of IL6 and TNFA (Figure 2G), similar to the training by b-glucan and oxLDL (Bekkering et al., 2014; Quintin et al., 2012).”
Developmental and Functional Heterogeneity of Monocytes. (2018, background): “The epigenetic changes associated with monocyte training involve histone modifications of genes encoding pro-inflammatory cytokines such as IL-6 and TNF but also genes of the mTOR pathway (Netea et al., 2016; Quintin et al., 2012).”
mTOR- and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity (2014, methodology): “Candida albicans and its main cell wall constituent, b-glucan, induce trained innate immune memory both in vitro and in vivo (7).”
Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity (2018, background): “This process involves changes in cell transcription and is designated ‘‘trained immunity’’ (Goodridge et al., 2016; Jensen et al., 2015; Netea and van Crevel, 2014; Netea et al., 2016; Quintin et al., 2012).”
Oxidized Low-Density Lipoprotein Induces Long-Term Proinflammatory Cytokine Production and Foam Cell Formation via Epigenetic Reprogramming of Monocytes (2014, methodology): “We have previously reported that training with β-glucan did not induce skewing of the macrophages into type M1 or M2 macrophages.(15) In addition, monocytes can also differentiate into dendritic cells (DCs), such as TNF and nitric oxide synthase–producing DCs.”
Trained immunity: a program of innate immune memory in health and disease (2016, background): “albicans or β-glucan enhanced their subsequent response to stimulation with unrelated pathogens or PAMPs, process termed as trained immunity (26).”