Glycerol Monolaurate Attenuated Immunological Stress and Intestinal Mucosal Injury by Regulating the Gut Microbiota and AMPK/NF-κB/Nrf2 Signaling Pathway in Lipopolysaccharide-Challenged Broilers

Background Antibiotic residues and resistance issues have led to the ban on antibiotic growth promoters in the poultry industry. Targeted dietary supplementation such as glycerol monolaurate (GML) has been found to ameliorate the negative effects of restriction on the use of antibiotic growth promoters by modulating the animal immune system and intestinal health. However, the mechanism by which GML contributes to the health and growth of broilers is indistinct. This study was conducted to investigate the effects of GML on immunity, intestinal barrier function, and cecal microbiota profiles in lipopolysaccharide (LPS)-challenged broilers. Results The results revealed that dietary GML intake augmented serum immunoglobulin A and G levels in LPS-challenged broilers. GML supplementation normalized LPS-induced variations in serum interleukin-6, interferon-γ, and LPS levels; jejunal villus height; and gene expression of interleukin-6, macrophage inflammatory protein-3α, toll-like receptor 4, nuclear factor kappa-B (NF-κB), caspase-1, tight junction proteins, adenosine monophosphate-activated protein kinase α1, nuclear factor-erythroid 2-related factor 2, and superoxide dismutase-1. GML administration ameliorated LPS-induced peroxidation by reducing malondialdehyde content and increasing antioxidant enzyme activity. Dietary GML intake enhanced the abundances of cecal probiotics such as Blautia, Lactobacillus, and Coprobacter in challenged broilers. The LPS-induced reduction in Anaerostipes, Pseudoflavonifractor, and Gordonibacter abundances in the cecum was inhibited by GML supplementation. Dietary GML intake was positively correlated with alterations in antioxidant enzyme activities and adenosine monophosphate-activated protein kinase (AMPK) α1, nuclear factor-erythroid 2-related factor 2 (Nrf2), and zonula occludens-1 levels. The genera Anaerostipes, Lachnospira, Gordonibacter, Lachnospira, Marvinbryantia, Peptococcus, and Pseudoflavonifractor were linked to attenuated inflammation and improved immunity and antioxidant capacity of LPS-challenged broilers. Conclusion Dietary GML intake alleviated LPS-induced immunological stress and intestinal injury in broilers. This beneficial effect of GML supplementation was attributed to the suppression of inflammation and oxidative stress by regulation of cecal microbiota and the AMPK/NF-κB/Nrf2 signaling pathway in LPS-challenged broilers.

Hematopoietic stem and progenitor cells improve survival from sepsis by boosting immunomodulatory cells

Sepsis accounts for 1 in 5 deaths worldwide, and new therapeutic strategies to reduce sepsis- related mortality are urgently needed. Since hematopoietic stem and progenitor cells (HSPCs) are responsible for producing blood and immune cells, including in response to immunological stress, we explored their potential for treating sepsis. In a mouse model of Group A Streptococcus (GAS)-induced sepsis, severe immunological stress was associated with significant depletion of bone marrow HSPCs and mortality within approximately 5-7 days. We hypothesized that the inflammatory environment of GAS infection drives rapid HSPC differentiation and depletion that can be rescued by infusion of donor HSPCs. Indeed, infusion of 10,000 naïve HSPCs into GAS-infected mice resulted in rapid myelopoiesis and a 50-60% increase in overall survival. Surprisingly, mice receiving donor HSPCs displayed a similar pathogen load compared to untreated mice. Flow cytometric analysis revealed a significantly increased number of myeloid-derived suppressor cells in HSPC-infused mice, which correlated with reduced inflammatory cytokine levels and restored HSPC levels. These findings suggest that HSPCs play an essential immunomodulatory role that may translate into new therapeutic strategies for sepsis.

MicroRNA expression profile in Lampetra morii upon Vibrio anguillarum infection and miR-4561 characterization targeting lip

As a critical evolutionary pivot between invertebrates and vertebrates, lampreys provide rich genetic information. Lamprey immune protein (LIP) is a key immune regulator. MicroRNAs, well-conserved in the response to immunological stress, remain understudied in lamprey immunity. We generated a lamprey microRNA expression atlas, using deep sequencing, upon Vibrio anguillarum infection. Using comparative methods, we found that miR-4561 potentially regulates innate immunity via interaction with lip. We found a sequence in the 3′-UTR region of LIP mRNA complementary to the miR-4561 seed region; miR-4561 expression was negatively correlated with LIP. During V. anguillarum infection, miR-4561 inhibited LIP expression and bacterial clearance. Notably, LIP expression in supraneural body cells was necessary for the Gram-negative immune response. Additionally, we observed that overexpression of miR-4561 induced apoptosis in embryonic cells, suggesting a role in embryonic development. Collectively, we show lamprey microRNAs may significantly affect gene regulation and provide new insights on LIP-mediated immune regulation.

Effects of Rhamnolipids on Growth Performance, Immune Function, and Cecal Microflora in Linnan Yellow Broilers Challenged with Lipopolysaccharides

This present study aimed to investigate the effects of rhamnolipids (RLS) on the growth performance, intestinal morphology, immune function, short-chain fatty acid content, and microflora community in broiler chickens challenged with lipopolysaccharides (LPS). A total of 450 broiler chickens were randomly allocated into three groups: basal diet with no supplement (NCO), basal diet with bacitracin (ANT), and basal diet with rhamnolipids (RLS). After 56 d of feeding, 20 healthy broilers were selected from each group, with half being intraperitoneally injected with lipopolysaccharides (LPS) and the other half with normal saline. Treatments with LPS were labelled LPS-NCO, LPS-ANT, and LPS-RLS, whereas treatments with normal saline were labelled NS-NCO, NS-ANT, and NS-RLS. LPS-challenged birds had lower jejunal villus height and higher crypt depth than unchallenged birds. LPS-RLS broilers had increased jejunal villus height and villus height/crypt depth ratio (V/C) but lower crypt depth than LPS-NCO. Dietary supplementation with RLS reduced the LPS-induced immunological stress. Compared with LPS-NCO, birds in LPS-RLS had lower concentrations of IL-1β, IL-6, and TNF-α. In LPS-challenged broilers, RLS and ANT increased the concentrations of IgA, IgM, and IgY compared with LPS-NCO. In LPS treatments, RLS enhanced the contents of acetic acid, butyrate, isobutyric acid, isovalerate, and valerate more than LPS-NCO birds. High-throughput sequencing indicated that RLS supplementation led to changes in the cecal microbial community of broilers. At the species level, Clostridium-sp-Marseille-p3244 and Slakia_eqcsolifaciens were more abundant in NS-RLS than in NS-NCO broilers. In summary, RLS improved the growth performance and relative abundance of cecal microbiota and reduced the LPS-induced immunological stress in broiler chickens.

Management and Handling of Commercial Crustaceans

Current crustacean production (~14 Mt) and value (up to USD60 billion) is significant and likely to increase further during the twenty-first century. Satisfactory management and handling of live crustaceans are important to safeguard the value, security, safety, and sustainability of wild-caught and aquaculture-sourced fisheries and increasingly to foster improved welfare and public perception of both industries. Decapod crustaceans are frequently transported live and internationally over long distances and experience anthropogenic stressors from point of capture to point of sale. Physical handling, emersion in air, and temperature fluctuations are key examples of stressors, which elicit progressive behavioral, physiological, and immunological stress responses in crustaceans. Stress responses are initiated to return the individual to a state of homeostasis; if these fail, then physiological collapse, a loss of vitality, and death will likely occur. There are several ways to mitigate the impact of stressors, reduce associated stress responses, and thus maintain quantity (survival, weight) and quality (vitality, sensorial perception) of live crustaceans. These include improved fishing techniques, better handling and operating procedures, and the introduction of proven equipment and facilities during the supply chain. The action of stressors and the effectiveness of potential mitigating strategies have been studied intensively via behavioral analysis and hemolymph sampling to ascertain changes in metabolites and the immune system. Finally, improved handling and management include global and ethical considerations, supported by relevant research, which may be achieved by adopting best practices and standards and by ensuring welfare and disease regulations.

Activator protein-1 transactivation of the major immediate early locus is a determinant of cytomegalovirus reactivation from latency

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that latently infects hematopoietic cells and has the ability to reactivate when triggered by immunological stress. This reactivation causes significant morbidity and mortality in immune-deficient patients, who are unable to control viral dissemination. While a competent immune system helps prevent clinically detectable viremia, a portrait of the factors that induce reactivation following the proper cues remains incomplete. Our understanding of the complex molecular mechanisms underlying latency and reactivation continues to evolve. We previously showed the HCMV-encoded G protein-coupled receptorUS28is expressed during latency and facilitates latent infection by attenuating the activator protein-1 (AP-1) transcription factor subunit, c-fos, expression and activity. We now show AP-1 is a critical component for HCMV reactivation. Pharmacological inhibition of c-fos significantly attenuates viral reactivation. In agreement, infection with a virus in which we disrupted the proximal AP-1 binding site in the major immediate early (MIE) enhancer results in inefficient reactivation compared to WT. Concomitantly, AP-1 recruitment to the MIE enhancer is significantly decreased following reactivation of the mutant virus. Furthermore, AP-1 is critical for derepression of MIE-driven transcripts and downstream early and late genes, while immediate early genes from other loci remain unaffected. Our data also reveal MIE transcripts driven from the MIE promoter, the distal promoter, and the internal promoter, iP2, are dependent upon AP-1 recruitment, while iP1-driven transcripts are AP-1–independent. Collectively, our data demonstrate AP-1 binding to and activation of the MIE enhancer is a key molecular process controlling reactivation from latency.

LIPOPOLYSACCHARIDE-INDUCED IMMUNOLOGICAL STRESS AT EARLY STAGES OF PREGNANCY AFFECTS THE DEVELOPMENT OF GONADOTROPIN RELEASING-HORMONE (GNRH)-PRODUCING SYSTEM

The aim of the present work was to study the development of afferent bonds between GnRH- and monoaminergic neurons in rat fetuses and to identify possible targets affected by LPS-induced inflammation. The innervation was analyzed using retrograde tracing method with DiI dye. At ED17 and ED21 olfactory bulbs (the area of GnRH migration) are innervated with monoaminergic neurons of septum and in lateral hypothalamus. The GnRH- and monoaminergic neuron interaction zones are sensitive to LPS (E. coli) prenatal exposure, which induces pro-inflammatory cytokine synthesis. We suppose that the olfactory bulbs of fetal forebrain can be a possible area of cytokine influence on GnRH- and monoaminergic neuron interaction.