Gut Microbiome and Organ Fibrosis

Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.

RESPON IMUN HOSPES TERHADAP INFEKSI Vibrio cholerae

The immune sistem is a way of the body’s defense sistem to save the host from the invasion of outside pathogen. Based on how respon to disease, that differentiated into two immune system are innate and adaptive system. Because it an cant throgh the stomach, these pathogenic bacteria go to the small intestin as a site infection. In the intestine, V. cholerae bactesia adhere and colonize and invasion to intestinal epihelial cells. Protection mechanism to V. cholerae are the natural defense presence of tick mucosa on the surface of epithelial cells can inhibit pathogene to adhere tointestinal epithelial cells. One anothet defense namely innate immune system did by phagocytic cells to attac pathogen agent and adaptive immune system involves IgA to opsonization so that can increase intestinal mucosal immune system

Histocompatibility and Reproduction: Lessons from the Anglerfish

Reproduction in certain deep-sea anglerfishes involves the permanent attachment of dwarf males to much larger females and fusion of their tissues leading to the establishment of a shared circulatory system. This unusual phenomenon of sexual parasitism enables anglerfishes to maximize reproductive success in the vast and deep oceans, where females and males otherwise rarely meet. An even more surprising phenomenon relates to the observation that joining of genetically disparate male and female anglerfishes does not evoke a strong anti-graft immune rejection response, which occurs in vertebrates following allogeneic parabiosis. Recent studies demonstrated that the evolutionary processes that led to the unique mating strategy of anglerfishes coevolved with genetic changes that resulted in loss of functional genes encoding critical components of the adaptive immune system. These genetic alterations enabled anglerfishes to tolerate the histoincompatible tissue antigens of their mate and prevent the occurrence of reciprocal graft rejection responses. While the exact mechanisms by which anglerfishes defend themselves against pathogens have not yet been deciphered, it is speculated that during evolution, anglerfishes adopted new immune strategies that compensate for the loss of B and T lymphocyte functions and enable them to resist infection by pathogens.

The Activated Macrophage – A Tough Fortress for Virus Invasion: How Viruses Strike Back

Macrophages (Mφ) are innate immune cells with a variety of functional phenotypes depending on the cytokine microenvironment they reside in. Mφ exhibit distinct activation patterns that are found within a wide array of activation states ranging from the originally discovered classical pro-inflammatory (M1) to the anti-inflammatory (M2) with their multi-facades. M1 cells are induced by IFNγ + LPS, while M2 are further subdivided into M2a (IL-4), M2b (Immune Complex) and M2c (IL-10) based on their inducing stimuli. Not surprisingly, Mφ activation influences the outcome of viral infections as they produce cytokines that in turn activate cells of the adaptive immune system. Generally, activated M1 cells tend to restrict viral replication, however, influenza and HIV exploit inflammation to support their replication. Moreover, M2a polarization inhibits HIV replication at the post-integration level, while HCMV encoded hrIL-10 suppresses inflammatory reactions by facilitating M2c formation. Additionally, viruses such as LCMV and Lassa Virus directly suppress Mφ activation leading to viral chronicity. Here we review how Mφ activation affects viral infection and the strategies by which viruses manipulate Mφ polarization to benefit their own fitness. An understanding of these mechanisms is important for the development of novel immunotherapies that can sway Mφ phenotype to inhibit viral replication.

HMGB1-Mediated Activation of the Inflammatory-Reparative Response Following Myocardial Infarction

Different cell types belonging to the innate and adaptive immune system play mutually non-exclusive roles during the different phases of the inflammatory-reparative response that occurs following myocardial infarction. A timely and finely regulation of their action is fundamental for the process to properly proceed. The high-mobility group box 1 (HMGB1), a highly conserved nuclear protein that in the extracellular space can act as a damage-associated molecular pattern (DAMP) involved in a large variety of different processes, such as inflammation, migration, invasion, proliferation, differentiation, and tissue regeneration, has recently emerged as a possible regulator of the activity of different immune cell types in the distinct phases of the inflammatory reparative process. Moreover, by activating endogenous stem cells, inducing endothelial cells, and by modulating cardiac fibroblast activity, HMGB1 could represent a master regulator of the inflammatory and reparative responses following MI. In this review, we will provide an overview of cellular effectors involved in these processes and how HMGB1 intervenes in regulating each of them. Moreover, we will summarize HMGB1 roles in regulating other cell types that are involved in the different phases of the inflammatory-reparative response, discussing how its redox status could affect its activity.

Ecological speciation promoted by divergent regulation of functional genes within African cichlid fishes

Rapid ecological speciation along depth gradients has taken place independently and repeatedly in freshwater fishes. While the extent of genomic divergence between ecomorphs is often well understood, the molecular mechanisms facilitating such rapid diversification are typically unclear. In Lake Masoko, an East African crater lake, the cichlid Astatotilapia calliptera has diverged into shallow littoral and deep benthic ecomorphs with strikingly different jaw structures within the last 1,000 years. Using genome-wide transcriptome data from jaw tissue, we explore two major regulatory transcriptional mechanisms, expression and splicing QTL variants and examine their contribution to differential gene expression underpinning functional phenotypes. We identified 7,550 genes with significant differential expression between ecomorphs, of which 4.2% were regulated by cis-regulatory expression QTLs, and 6.4% were regulated by cis-regulatory splicing QTLs. There were also strong signals of divergent selection of differentially expressed genes that showed divergent regulation from expression, splicing or both QTL variants, including genes associated with major jaw plasticity and adaptation networks, adaptive immune system response, and oxidoreductase processes. These results suggest that transcriptome plasticity and modification have important roles during early-stage ecological speciation and demonstrate the role of regulatory-variants as important targets of selection driving ecologically-relevant divergence in gene expression that is associated with adaptive diversification.

Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets

It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of genetic homeostasis, supports multicellularity, and protects an organism from different pathogens at a qualitatively different level than innate immunity. This seemingly simple property is based on millions of years of evolution that led to the formation of diversification mechanisms of antigen-recognizing receptors and later to the emergence of a system of presentation of the self and non-self antigens. The latter could have a crucial significance because the presentation of nearly complete diversity of auto-antigens in the thymus allows for the “calibration” of the forming repertoires of T-cells for the recognition of self, altered-self, and non-self antigens that are presented on the periphery. The central role in this process belongs to promiscuous gene expression by the thymic epithelial cells that express nearly the whole spectrum of proteins encoded in the genome, meanwhile maintaining their cellular identity. This complex mechanism requires strict control that is executed by several transcription factors. One of the most important of them is AIRE. This noncanonical transcription factor not only regulates the processes of differentiation and expression of peripheral tissue-specific antigens in the thymic medullar epithelial cells but also controls intercellular interactions in the thymus. Besides, it participates in an increase in the diversity and transfer of presented antigens and thus influences the formation of repertoires of maturing thymocytes. Due to these complex effects, AIRE is also called a transcriptional regulator. In this review, we briefly described the history of AIRE discovery, its structure, functions, and role in the formation of antigen-recognizing receptor repertoires, along with other transcription factors. We focused on the phylogenetic prerequisites for the development of modern adaptive immunity and emphasized the importance of the antigen presentation system.

Ancestral SARS-CoV-2-specific T cells cross-recognize Omicron (B.1.1.529)

The emergence of the SARS-CoV-2 variant-of-concern Omicron (B.1.1.529) has destabilized global efforts to control the impact of COVID-19. Recent data have suggested that B.1.1.529 can readily infect people with naturally acquired or vaccine-induced immunity, facilitated in some cases by viral escape from antibodies that neutralize ancestral SARS-CoV-2. However, severe disease appears to be relatively uncommon in such individuals, highlighting a potential role for other components of the adaptive immune system. We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection and, more extensively, by mRNA vaccination provide comprehensive heterologous immune reactivity against B.1.1.529. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike-reactive CD4+ and CD8+ T cells exhibited similar functional attributes, memory distributions, and phenotypic traits in response to the ancestral strain or B.1.1.529. Our data indicate that established SARS-CoV-2 spike-specific CD4+ and CD8+ T cell responses, especially after mRNA vaccination, remain largely intact against B.1.1.529.

Molecular mechanisms of liver carcinogenesis related to metabolic syndrome

Global prevalence of non-alcoholic fatty liver disease (NAFLD) and of NAFLD-hepatocellular carcinoma (HCC) is estimated to grow in the next years. The burden of NAFLD and the evidence that NAFLD-HCC arises also in non-cirrhotic patients, explain the urgent need of a better characterization of the molecular mechanisms involved in NAFLD progression. Obesity and diabetes cause a chronic inflammatory state which favors changes in serum cytokines and adipokines, an increase in oxidative stress, DNA damage, and the activation of multiple signaling pathways involved in cell proliferation. Moreover, a role in promoting NAFLD-HCC has been highlighted in the innate and adaptive immune system, dysbiosis, and alterations in bile acids metabolism. Several dietary, genetic, or combined mouse models have been used to study nonalcoholic steatohepatitis (NASH) development and its progression to HCC, but models that fully recapitulate the biological and prognostic features of human NASH are still lacking. In humans, four single nucleotide polymorphisms (PNPLA3, TM6SF2, GCKR, and MBOAT7) have been linked to the development of both NASH and HCC in cirrhotic and non-cirrhotic patients, whereas HSD17B13 polymorphism has a protective effect. In addition, higher rates of somatic ACVR2A mutations and a novel mutational signature have been recently discovered in NASH-HCC patients. The knowledge of the molecular pathogenesis of NAFLD-HCC will be helpful to personalized screening programs and allow for primary and secondary chemopreventive treatments for NAFLD patients who are more likely to progress to HCC.

Acute Cerebellitis and Myeloradiculitis Associated With SARS-CoV-2 Infection in Common Variable Immunodeficiency—A Case Report

The role of the adaptive immune system in mediating COVID-19 is largely unknown. Therefore, it is difficult to predict the clinical course in patients with common variable immunodeficiency (CVID), a disease characterized by dysfunctional lymphocytes and impaired antibody production. We report a case of SARS-CoV-2 infection presenting as isolated neurological symptoms in a patient with CVID. The patient subsequently improved following steroids, intravenous immunoglobulin, and convalescent plasma (CP). The latter has been shown to be safe and efficacious in treating COVID-19 in patients with primary immunodeficiency. Recent data suggest that the mechanism of CNS injury in COVID-19 may be due to immunological dysregulation rather than direct viral-mediated injury. This case exemplifies the complex interaction between the brain, the immune system, and the SARS-CoV-2 virus.