DNA Synthesis Is Activated in Mosquitoes and Human Monocytes During the Induction of Innate Immune Memory.

Benito Recio-Totoro,Valeria Vargas-Ponce de León,Ramon Moreno-Torres,Rob J. W. Arts,Jorge Cime-Castillo,Humberto Lanz-Mendoza,Fabiola Claudio-Piedras,Mihai G. Netea,Salvador Hernández-Martínez

doi:10.3389/fimmu.2018.02834

Abstract

Endoreplication is a cell cycle program in which cells replicate their genomes without undergoing mitosis and cytokinesis. For the normal development of many organisms (from fungi to humans) and the formation of their organs, endoreplication is indispensable. The aim of the present study was to explore whether endoreplication and DNA synthesis are relevant processes during the induction of trained innate immunity in human monocytes and in the Anopheles albimanus mosquito cell line. During the induction of trained immunity in both models, endoreplication markers were overexpressed and we observed an increase in DNA synthesis with an augmented copy number of genes essential for trained immunity. Blocking DNA synthesis prevented trained immunity from being established. Overall, these findings suggest that DNA synthesis and endoreplication are important mechanisms involved in inducing innate immune memory. They have probably been conserved throughout evolution from invertebrates to humans.

Highlights

Both old and recent studies have demonstrated that innate immunity is able to adapt in vertebrates, invertebrates, and plants upon encountering an infection, representing a de facto innate immune memory [see review for invertebrates [1], plants [2], and vertebrates [3, 4]]
In order to test for a possible role of endoreplication in the mosquito cell line during the establishment of trained immunity (TI), cells were cultivated in the presence of Zymosan or the P. berghei extract
BrdU incorporation was elevated in cells exposed to Zymosan or the parasite extract, suggesting that endoreplication had been stimulated (Figure 1C)

Summary

Introduction

Both old and recent studies have demonstrated that innate immunity is able to adapt in vertebrates, invertebrates, and plants upon encountering an infection, representing a de facto innate immune memory [see review for invertebrates [1], plants [2], and vertebrates [3, 4]]. Monocytes can be trained by pre-exposure to β-glucan of Candida albicans or the BCG vaccine, leading in both cases to an enhanced and long-lasting response to microbial components at a later time [6,7,8]. This is the result of epigenetic histone changes at the level of H3K27ac and H3K4me3 [5]. Epigenetic reprogramming is known to participate in systemic acquired resistance, a process of epigenetic-induced immune memory in plants [2]

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