Balancing Selection Pressures, Multiple Objectives, and Neural Modularity to Coevolve Cooperative Agent Behavior

Previous research using evolutionary computation in Multi-Agent Systems indicates that assigning fitness based on team vs.\ individual behavior has a strong impact on the ability of evolved teams of artificial agents to exhibit teamwork in challenging tasks. However, such research only made use of single-objective evolution. In contrast, when a multiobjective evolutionary algorithm is used, populations can be subject to individual-level objectives, team-level objectives, or combinations of the two. This paper explores the performance of cooperatively coevolved teams of agents controlled by artificial neural networks subject to these types of objectives. Specifically, predator agents are evolved to capture scripted prey agents in a torus-shaped grid world. Because of the tension between individual and team behaviors, multiple modes of behavior can be useful, and thus the effect of modular neural networks is also explored. Results demonstrate that fitness rewarding individual behavior is superior to fitness rewarding team behavior, despite being applied to a cooperative task. However, the use of networks with multiple modules allows predators to discover intelligent behavior, regardless of which type of objectives are used

Pathways Involved in Recognition and Induction of Trained Innate Immunity by Plasmodium falciparum

Malarial infection in naïve individuals induces a robust innate immune response, but our understanding of the mechanisms by which the innate immune system recognizes malaria and regulates its response remain incomplete. Our group previously showed that stimulation of macrophages with Plasmodium falciparum genomic DNA (gDNA) and AT-rich oligodeoxynucleotides (ODNs) derived from this gDNA induces the production of type I interferons (IFN-I) through a STING/TBK1/IRF3-dependent pathway; however, the identity of the upstream cytosolic DNA receptor remained elusive. Here, we demonstrate that this IFN-I response is dependent on cyclic GMP-AMP synthase (cGAS). cGAS produced the cyclic dinucleotide 2’3’-cGAMP in response to P. falciparum gDNA and AT-rich ODNs, inducing IRF3 phosphorylation and IFNB transcription. In the recently described model of innate immune memory, an initial stimulus primes the innate immune system to either hyperrespond (termed “training”) or hyporespond (“tolerance”) to subsequent immune challenge. Previous work in mice and humans demonstrated that infection with malaria can both serve as a priming stimulus and promote tolerance to subsequent infection. In this study, we demonstrate that initial stimulation with P. falciparum-infected red blood cells (iRBCs) or the malaria crystal hemozoin (Hz) induced human adherent peripheral blood mononuclear cells (PBMCs) to hyperrespond to subsequent Toll-like receptor (TLR) challenge. This hyperresponsiveness correlated with increased H3K4me3 at important immunometabolic promoters, and these epigenetic modifications were also seen in monocytes from Kenyan children naturally infected with malaria. However, the use of epigenetic and metabolic inhibitors indicated that malaria-induced trained immunity may occur via previously unrecognized mechanism(s)

RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA

Recognition of DNA and RNA molecules derived from pathogens or self-antigen is one way the mammalian immune system senses infection and tissue damage. Activation of immune signaling receptors by nucleic acids is controlled by limiting the access of DNA and RNA to intracellular receptors, but the mechanisms by which endosome-resident receptors encounter nucleic acids from the extracellular space are largely undefined. In this study, we show that the receptor for advanced glycation end-products (RAGE) promoted DNA uptake into endosomes and lowered the immune recognition threshold for the activation of Toll-like receptor 9, the principal DNA-recognizing transmembrane signaling receptor. Structural analysis of RAGE-DNA complexes indicated that DNA interacted with dimers of the outermost RAGE extracellular domains, and could induce formation of higher-order receptor complexes. Furthermore, mice deficient in RAGE were unable to mount a typical inflammatory response to DNA in the lung, indicating that RAGE is important for the detection of nucleic acids in vivo