Cd59 and inflammation orchestrate Schwann cell development

Efficient neurotransmission is essential for organism survival and is enhanced by myelination. However, the genes that regulate myelin and myelinating glial cell development have not been fully characterized. Data from our lab and others demonstrates that cd59, which encodes for a small GPI-anchored glycoprotein, is highly expressed in developing zebrafish, rodent, and human oligodendrocytes (OLs) and Schwann cells (SCs), and that patients with CD59 dysfunction develop neurological dysfunction during early childhood. Yet, the function of CD59 in the developing nervous system is currently undefined. In this study, we demonstrate that cd59 is expressed in a subset of developing SCs. Using cd59 mutant zebrafish, we show that developing SCs proliferate excessively, which leads to reduced myelin volume, altered myelin ultrastructure, and perturbed node of Ranvier assembly. Finally, we demonstrate that complement activity is elevated in cd59 mutants and that inhibiting inflammation restores SC proliferation, myelin volume, and nodes of Ranvier to wildtype levels. Together, this work identifies Cd59 and developmental inflammation as key players in myelinating glial cell development, highlighting the collaboration between glia and the innate immune system to ensure normal neural development.

Innate Immune System Response to Burn Damage—Focus on Cytokine Alteration

In the literature, burns are understood as traumatic events accompanied by increased morbidity and mortality among affected patients. Their characteristic feature is the formation of swelling and redness at the site of the burn, which indicates the development of inflammation. This reaction is not only important in the healing process of wounds but is also responsible for stimulating the patient’s innate immune system. As a result of the loss of the protective ability of the epidermis, microbes which include bacteria, fungi, and viruses have easier access to the system, which can result in infections. However, the patient is still able to overcome the infections that occur through a cascade of cytokines and growth factors stimulated by inflammation. Long-term inflammation also has negative consequences for the body, which may result in multi-organ failure or lead to fibrosis and scarring of the skin. The innate immune response to burns is not only immediate, but also severe and prolonged, and some people with burn shock may also experience immunosuppression accompanied by an increased susceptibility to fatal infections. This immunosuppression includes apoptosis-induced lymphopenia, decreased interleukin 2 (IL-2) secretion, neutrophil storm, impaired phagocytosis, and decreased monocyte human leukocyte antigen-DR. This is why it is important to understand how the immune system works in people with burns and during infections of wounds by microorganisms. The aim of this study was to characterize the molecular pathways of cell signaling of the immune system of people affected by burns, taking into account the role of microbial infections.

Complement cascade inhibition in geographic atrophy: a review

The pathophysiology of dry age-related macular degeneration (AMD) and specifically geographic atrophy (GA) has been linked to the complement cascade. This cascade is part of the innate immune system and is made up of the classical, alternative, and lectin pathways. The pathways comprise a system of plasma and membrane-associated serum proteins that are activated with identification of a nonself entity. A number of these proteins have been implicated in the development and progression of dry AMD. The three pathways converge at C3 and cascade down through C5, making both of these proteins viable targets for the treatment of dry AMD. In addition, there are a number of complement factors, CFB, CFD, CFH, and CFI, which are potential therapeutic targets as well. Several different complement-directed therapeutics are being studied for the treatment of dry AMD with the hope that one of these approaches will emerge as the first approved treatment for GA.

LAPped in Proof: LC3‐Associated Phagocytosis and the Arms Race Against Bacterial Pathogens

Cells of the innate immune system continuously patrol the extracellular environment for potential microbial threats that are to be neutralized by phagocytosis and delivery to lysosomes. In addition, phagocytes employ autophagy as an innate immune mechanism against pathogens that succeed to escape the phagolysosomal pathway and invade the cytosol. In recent years, LC3-associated phagocytosis (LAP) has emerged as an intermediate between phagocytosis and autophagy. During LAP, phagocytes target extracellular microbes while using parts of the autophagic machinery to label the cargo-containing phagosomes for lysosomal degradation. LAP contributes greatly to host immunity against a multitude of bacterial pathogens. In the pursuit of survival, bacteria have developed elaborate strategies to disarm or circumvent the LAP process. In this review, we will outline the nature of the LAP mechanism and discuss recent insights into its interplay with bacterial pathogens.

Cytokine storm interference

Viral infections are a natural and inevitable part of life. In healthy individuals, mortality increases when the body’s innate immune system quickly activates, creating a cytokine storm. A rapid and excessive release of cytokines into the bloodstream can cause acute respiratory distress syndrome and death. This communication proposes inhibiting cytokine storm development through forced atopy. Hyper-allergenic skin cream therapy stimulates adaptive immunity to support innate immunity before acute infection.

Retrovirus-derived acquired genes, RTL5 and RTL6, are novel constituents of the innate immune system in the eutherian brain.

Retrotransposon Gag-like 5 (RTL5, also known as sushi-ichi-related retrotransposon homolog 8 (SIRH8)) and RTL6 (aka SIRH3) are eutherian-specific genes presumably derived from a retrovirus and phylogenetically related to each other. RTL5 encodes a strongly acidic protein while RTL6 encodes an extremely basic protein, and the former is well conserved and the latter extremely well conserved among the eutherians, indicating their unique and critically important roles as acquired genes. Here we report that RTL5 and RTL6 are microglial genes playing roles in the front line of brain innate immune responses against distinct pathogens. Venus and mCherry knock-in mice exhibited expression of RTL5-mCherry and RTL6-Venus fusion proteins in microglia and as extracellular granules in the central nervus system (CNS), and displayed a rapid response to pathogens such as lipopolysaccharide (LPS), double-stranded (ds) RNA analog and non-methylated CpG DNA. These proteins trapped pathogens in microglia in a variety of RTL-pathogen complexes depending on the pathogens. These results demonstrate that RTL5 and RTL6 exert functional effects against different hazardous substances cooperatively and/or independently to protect the developing and/or mature brain. This provides the first evidence that retrovirus-derived genes play a role in the innate immune system of the eutherian brain.