Glucocorticoid-mediated Suppression of Effector Programming Assists the Memory Transition of Virus-specific CD8+ T Cells.

We demonstrate the role of signaling via the glucocorticoid receptor, NR3C1, in differentiation of CD8+ T cell memory. Pharmacological inhibition as well as the short hairpin RNA-mediated knockdown of the receptor hindered memory transition and limited the homeostatic turnover of the activated CD8+ T cells. Dexamethasone exposure of CD8+ T cells expanded during a resolving infection with influenza A virus or a γ-herpesvirus promoted conversion of effector cells into memory cells by modulating cellular metabolism and lowering the accumulation of reactive oxygen species.

RelA-mediated signaling connects adaptation to chronic cardiomyocyte stress with myocardial and systemic inflammation in the ADCY8 model of accelerated aging.

Mice with cardiac-specific overexpression of adenylyl cyclase (AC) type 8 (TG) are under a constant state of severe myocardial stress. They have a remarkable ability to adapt to this stress, but they eventually develop accelerated cardiac aging and experience reduced longevity. We have previously demonstrated through bioinformatics that constitutive adenylyl cyclase activation in TG mice is associated with the activation of inflammation-related signaling pathways.

Cardiomyocyte-specific adenylyl cyclase type-8 overexpression induces activation of RelA together with myocardial and systemic inflammation.

Background: Mice with cardiac-specific overexpression of adenylyl cyclase (AC) type 8 (TG ) are under a constant state of severe myocardial stress. They have a remarkable ability to adapt to this stress, but they eventually develop accelerated cardiac aging and experience reduced longevity.

Results: Here we demonstrate that activation of ACVIII in cardiomyocytes results in cell-autonomous RelA-mediated NF-κB signaling.

Loss of CD4 T cell-intrinsic arginase 1 accelerates Th1 response kinetics and reduces lung pathology during influenza infection.

Arginase 1 (Arg1), the enzyme catalyzing the conversion of arginine to ornithine, is a hallmark of IL-10-producing immunoregulatory M2 macrophages. However, its expression in T cells is disputed. Here, we demonstrate that induction of Arg1 expression is a key feature of lung CD4 T cells during mouse in vivo influenza infection.

C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection.

Systemic candidiasis is a common, high-mortality, nosocomial fungal infection. Unexpectedly, it has emerged as a complication of anti-complement C5-targeted monoclonal antibody treatment, indicating a critical niche for C5 in antifungal immunity. We identified transcription of complement system genes as the top biological pathway induced in candidemic patients and as predictive of candidemia.

Non-coding RNAs in immunoregulation and autoimmunity: Technological advances and critical limitations.

Immune cell function is critically dependent on precise control over transcriptional output from the genome. In this respect, integration of environmental signals that regulate gene expression, specifically by transcription factors, enhancer DNA elements, genome topography and non-coding RNAs (ncRNAs), are key components. The first three have been extensively investigated.

Autocrine vitamin D signaling switches off pro-inflammatory programs of T1 cells.

The molecular mechanisms governing orderly shutdown and retraction of CD4 type 1 helper T (T1) cell responses remain poorly understood. Here we show that complement triggers contraction of T1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated the transition from pro-inflammatory interferon-γ T1 cells to suppressive interleukin-10 cells.

Host-Virus Chimeric Events in SARS-CoV-2-Infected Cells Are Infrequent and Artifactual.

The pathogenic mechanisms underlying severe SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection remain largely unelucidated. High-throughput sequencing technologies that capture genome and transcriptome information are key approaches to gain detailed mechanistic insights from infected cells. These techniques readily detect both pathogen- and host-derived sequences, providing a means of studying host-pathogen interactions.

Host-virus chimeric events in SARS-CoV2 infected cells are infrequent and artifactual.

Pathogenic mechanisms underlying severe SARS-CoV2 infection remain largely unelucidated. High throughput sequencing technologies that capture genome and transcriptome information are key approaches to gain detailed mechanistic insights from infected cells. These techniques readily detect both pathogen and host-derived sequences, providing a means of studying host-pathogen interactions.

Divergent Effects of a Transient Corticosteroid Therapy on Virus-Specific Quiescent and Effector CD8 T Cells.

We investigated the influence of a transient treatment of corticosteroid on CD8 T cells during herpesvirus infection. Dexamethasone, a synthetic corticosteroid, induced apoptosis of naïve and memory CD8 T cells but virus-specific effector cells were spared. CD8 T cell susceptibility was directly correlated with the expression of nr3c1.

Galectin-3 Regulates γ-Herpesvirus Specific CD8 T Cell Immunity.

To gain insights into the molecular mechanisms and pathways involved in the activation of γ-herpesvirus (MHV68)-specific T cell receptor transnuclear (TN) CD8 T cells, we performed a comprehensive transcriptomic analysis. Upon viral infection, we observed differential expression of several thousand transcripts encompassing various networks and pathways in activated TN cells compared with their naive counterparts. Activated cells highly upregulated galectin-3.

Herpesviruses: Harmonious Pathogens but Relevant Cofactors in Other Diseases?

Most vertebrates are infected with one or more herpesviruses and remain so for the rest of their lives. The relationship of immunocompetent healthy host with herpesviruses may sometime be considered as harmonious. However, clinically severe diseases can occur when host immunity is compromised due to aging, during some stress response, co-infections or during neoplastic disease conditions.