In mammalian species, pregnancy is a complex process that involves the maternal recognition of pregnancy, implantation, decidualization, placentation, and parturition. The innate immune system is composed of cellular components, such as natural killer cells, neutrophils, monocytes, and macrophages, and effector molecules, such as cytokines, interferons, antimicrobial peptides, and complement components. The innate immune system plays a critical role as the first line of defense against infection or inflammation to maintain homeostasis and activate the adaptive immunity. During pregnancy, innate immune cells and effector molecules act on the regulation of innate immunity for host defense and processes such as embryo development, implantation, and placentation at the maternal-conceptus interface. In this review, we describe the components of the innate immune system and their functions at the maternal-conceptus interface to establish and maintain pregnancy in animal species that form hemochorial- or epitheliochorial-type placentas, including humans, rodents, ruminants, and pigs.

The first line of defense against invading pathogens usually relies on innate immune systems. In this context, the recognition of exogenous RNA structures is primordial to fight, notably, against RNA viruses. One of the most efficient immune response pathways is based on the sensing of RNA double helical motifs by the oligoadenylate synthase (OAS) proteins, which in turn triggers the activity of RNase L and, thus, cleaves cellular and viral RNA. In this contribution, by using long-range molecular dynamics simulations, complemented with enhanced sampling techniques, we elucidate the structural features leading to the activation of OAS by interaction with a model double-strand RNA oligomer mimicking a viral RNA. We characterize the allosteric regulation induced by the nucleic acid leading to the population of the active form of the protein. Furthermore, we also identify the free energy profile connected to the active vs. inactive conformational transitions in the presence and absence of RNA. Finally, the role of two RNA mutations, identified as able to downregulate OAS activation, in shaping the protein/nucleic acid interface and the conformational landscape of OAS is also analyzed.

Neuroinflammation is a key component underlying multiple neurological disorders, yet non-invasive and cost-effective assessment of in vivo neuroinflammatory processes in the central nervous system remains challenging. Diffusion weighted magnetic resonance spectroscopy (dMRS) has shown promise in addressing these challenges by measuring diffusivity properties of different neurometabolites, which can reflect cell-specific morphologies. Prior work has demonstrated dMRS utility in capturing microglial reactivity in the context of lipopolysaccharide (LPS) challenges and serious neurological disorders, detected as changes of microglial metabolite diffusivity properties. However, the extent to which such dMRS metrics are capable of detecting subtler and more nuanced levels of neuroinflammation in populations without overt neuropathology is unknown. Here we examined the relationship between intrinsic, gut-derived levels of systemic LPS and dMRS-based apparent diffusion coefficients (ADC) of choline, creatine, and N-acetylaspartate (NAA) in two brain regions: the thalamus and the corona radiata. Higher plasma LPS concentrations were significantly associated with increased ADC of choline and NAA in the thalamic region, with no such relationships observed in the corona radiata for any of the metabolites examined. As such, dMRS may have the sensitivity to measure microglial reactivity across populations with highly variable levels of neuroinflammation, and holds promising potential for widespread applications in both research and clinical settings.

The direct interplay between the immune and nervous systems is now well established. Within the brain, these interactions take place between neurons and resident glial cells, i.e., microglia and astrocytes, or infiltrating immune cells, influenced by systemic factors. A special form of physical cell-cell interactions is the so-called \"neuroimmunological (NI) synapse.\" There is compelling evidence that the same signaling pathways that regulate inflammatory responses to injury or ischemia also play potent roles in brain development, plasticity, and function. Proper synaptic wiring is as important during development as it is during disease states, as it is necessary for activity-dependent refinement of neuronal circuits. Since the process of forming synaptic connections in the brain is highly dynamic, with constant changes in strength and connectivity, the immune component is perfectly suited for the regulatory task as it is in constant turnover. Many cellular and molecular players in this interaction remain to be uncovered, especially in pathological states. In this review, we discuss and propose possible communication hubs between components of the adaptive and innate immune systems and the synaptic element in ischemic stroke pathology.

Transcription factors (TFs) have an important role in the regulation of the gene expression network. The role of TFs in the immune response of freshwater crayfish is poorly understood, but leveraging the regulatory mechanisms of immune response could augment the resistance against the invasive oomycete pathogen, Aphanomyces astaci. Previous studies indicated that the TFs CCAAT/enhancer-binding protein (C/EBP) and putative Krüppel homolog-1 protein (Kr-h1) might play a role in immune and stress response of the noble crayfish (Astacus astacus). Here, we aimed to further characterise these two gene products to gain a better understanding of their evolutionary origin, domain organisation and expression patterns across different crayfish tissues. Furthermore, we conducted an immune stimulation experiment to observe the potential changes in the gene expression of C/EBP and Kr-h1 under immune challenge in different crayfish tissues. Our results showed that both C/EBP and Kr-h1 are closely related to other C/EBPs and Kr-h1s in Malacostraca. Gene expression analysis revealed that both TFs are present in all analysed tissues, with higher expression of C/EBP in the gills and Kr-h1 in the abdominal muscle. Immune stimulation with laminarin (mimicking β-1-3-glucan in the oomycete cell wall) showed an activation of the crayfish immune system, with an overall increase in the total haemocyte count (THC) compared to untreated control and crayfish buffered saline (CBS) treatment. On the gene expression level, an up-regulation of the C/EBP gene was detected in the laminarin treated group in hepatopancreas and heart, while no changes were observed for the Kr-h1 gene. Our results indicate an early change in C/EBP expression in multiple tissues during immune stimulation and suggest its involvement in the immune response of the noble crayfish.

UNASSIGNED: To explore the underlying mechanisms the airway microbiome contributes to Acute Exacerbation of Chronic Obstructive Pulmonary Disease(AECOPD).
UNASSIGNED: We enrolled 31 AECOPD patients and 26 stable COPD patients, their sputum samples were collected for metagenomic and RNA sequencing, and then subjected to bioinformatic analyses. The expression of host genes was validated by Quantitative Real-time PCR(qPCR) using the same batch of specimens.
UNASSIGNED: Our results indicated a higher expression of Rothia mucilaginosa(p=0.015) in the AECOPD group and Haemophilus influenzae(p=0.005) in the COPD group. The Different expressed genes(DEGs) detected were significantly enriched in \"type I interferon signaling pathway\"(p<0.001, q=0.001) in gene function annotation, and \"Cytosolic DNA-sensing pathway\"(p=0.002, q=0.024), \"Toll-like receptor signaling pathway\"(p=0.006, q=0.045), and \"TNF signaling pathway\"(p=0.006, q=0.045) in KEGG enrichment analysis. qPCR amplification experiment verified that the expression of OASL and IL6 increased significantly in the AECOPD group.
UNASSIGNED: Pulmonary bacteria dysbiosis may regulate the pathogenesis of AECOPD through innate immune system pathways like type I interferon signaling pathway and Toll-like receptor signaling pathway.

The qseC gene is a two-component system that encodes a histidine protein kinase and is highly conserved among different Glaesserella parasuis strains. In this study, we used qRT-PCR and enzyme-linked immunosorbent assay to confirm that Toll-like receptor 4 (TLR4) plays a role in the expression of proinflammatory cytokines interleukin (IL)-1β and IL-6 by stimulating RAW 264.7 macrophages with QseC. Furthermore, we revealed that blocking the p38 and NF-κB pathways that regulate signaling can significantly reduce the production of proinflammatory cytokines induced by QseC. In summary, our data suggest that QseC is a novel proinflammatory mediator that induces TLR4-dependent proinflammatory activity in RAW 264.7 macrophages through the p38 and NF-κB pathways.

The immune system of ticks, along with that of other invertebrates, is comparatively simpler than that of vertebrates, relying solely on innate immune responses. Direct antimicrobial defence is provided by the synthesis of antimicrobial peptides (AMPs), including defensins. The aim of this study was to investigate the differences in defensin genes expression between questing and engorged Ixodes ricinus (def1 and def2) and Dermacentor reticulatus (defDr) ticks, in the presence of selected pathogens: Borrelia spp., Rickettsia spp., Babesia spp., Anaplasma phagocytophilum, and Neoehrlichia mikurensis in the natural environment. After pathogen screening by PCR/qPCR, the expression of defensin genes in pathogen positive ticks and ticks without any of the tested pathogens, was analysed by reverse transcription qPCR. The results showed an increased expression of defensin genes in I. ricinus ticks after blood feeding and I. ricinus and D. reticulatus ticks during in cases of co-infection. In particular, the expression of defensins genes was higher in questing D. reticulatus than in questing and engorged I. ricinus ticks, when borreliae were detected. This study contributes to uncovering the expression patterns of defensin genes in the presence of several known tick pathogens, the occurrence of these pathogens and possible regulatory mechanisms of defensins in tick vector competence.

Atherosclerotic vascular disease disproportionately affects persons living with HIV (PLWH) compared to those without. The reasons for the excess risk include dysregulated immune response and inflammation related to HIV infection itself, comorbid conditions, and co-infections. Here, we review an updated understanding of immune and inflammatory pathways underlying atherosclerosis in PLWH, including effects of viral products, soluble mediators and chemokines, innate and adaptive immune cells, and important co-infections. We also present potential therapeutic targets which may reduce cardiovascular risk in PLWH.

Organ transplantation is characterized by a sequence of steps that involve operative trauma, organ preservation, and ischemia-reperfusion injury in the transplant recipient. During this process, the release of damage-associated molecular patterns (DAMPs) promotes the activation of innate immune cells via engagement of the toll-like receptor (TLR) system, the complement system, and coagulation cascade. Different classes of effector responses are then carried out by specialized populations of macrophages, dendritic cells, and T and B lymphocytes; these play a central role in the orchestration and regulation of the inflammatory response and modulation of the ensuing adaptive immune response to transplant allografts. Organ function and rejection of human allografts have traditionally been studied through the lens of adaptive immunity; however, an increasing body of work has provided a more comprehensive picture of the pivotal role of innate regulation of adaptive immune responses in transplant and the potential therapeutic implications. Herein we review literature that examines the repercussions of inflammatory injury to transplantable organs. We highlight novel concepts in the pathophysiology and mechanisms involved in innate control of adaptive immunity and rejection. Furthermore, we discuss existing evidence on novel therapies aimed at innate immunomodulation and how this could be harnessed in the transplant setting.