scholarly journals Type I interferons protect neonates from acute inflammation through interleukin 10–producing B cells

2007 ◽  
Vol 204 (5) ◽  
pp. 1107-1118 ◽  
Author(s):  
Xiaoming Zhang ◽  
Edith Deriaud ◽  
Xinan Jiao ◽  
Deborah Braun ◽  
Claude Leclerc ◽  
...  
Keyword(s):  
B Cells ◽  
Bacterial Infections ◽  
Acute Inflammation ◽  
Inflammatory Responses ◽  
Underlying Mechanism ◽  
Interleukin 10 ◽  
Type I Interferons ◽  
Type I ◽  
Dependent Manner ◽  
Antiinflammatory Property

Newborns and infants are highly susceptible to viral and bacterial infections, but the underlying mechanism remains poorly understood. We show that neonatal B cells effectively control the production of proinflammatory cytokines by both neonatal plasmacytoid and conventional dendritic cells, in an interleukin (IL) 10–dependent manner, after Toll-like receptor (TLR) 9 triggering. This antiinflammatory property of neonatal B cells may extend to other TLR agonists (Pam3CSK4, lipopolysaccharide, and R848) and viruses. In the absence of B cells or of CD5+ B cell subsets, neonatal mice developed stronger inflammatory responses and became lethally susceptible to CpG challenge after galactosamine sensitization, whereas wild-type (WT) mice were resistant. Paradoxically, interferon (IFN)-α/β enhanced the inflammatory response to CpG challenge in adult mice, whereas they helped to control neonatal acute inflammation by stimulating the secretion of IL-10 by neonatal B cells. Finally, WT neonatal B cells rescued IL-10−/− neonates from a lethal CpG challenge, whereas IFN-α/β receptor–deficient B cells did not. Our results show that type I IFNs support a negative regulatory role of neonatal B cells on TLR-mediated inflammation, with important implications for neonatal inflammation and infection.

scholarly journals Impact of STING Inflammatory Signaling during Intracellular Bacterial Infections

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 74
Author(s):  
Erika S. Guimarães ◽  
Fabio V. Marinho ◽  
Nina M. G. P. de Queiroz ◽  
Maísa M. Antunes ◽  
Sergio C. Oliveira
Keyword(s):  
Immune Responses ◽  
Bacterial Infections ◽  
Inflammatory Responses ◽  
Metabolic Reprogramming ◽  
Host Cells ◽  
Type I Interferons ◽  
Type I ◽  
Bacterial Survival ◽  
Inflammatory Profile ◽  
The Impact

The early detection of bacterial pathogens through immune sensors is an essential step in innate immunity. STING (Stimulator of Interferon Genes) has emerged as a key mediator of inflammation in the setting of infection by connecting pathogen cytosolic recognition with immune responses. STING detects bacteria by directly recognizing cyclic dinucleotides or indirectly by bacterial genomic DNA sensing through the cyclic GMP-AMP synthase (cGAS). Upon activation, STING triggers a plethora of powerful signaling pathways, including the production of type I interferons and proinflammatory cytokines. STING activation has also been associated with the induction of endoplasmic reticulum (ER) stress and the associated inflammatory responses. Recent reports indicate that STING-dependent pathways participate in the metabolic reprogramming of macrophages and contribute to the establishment and maintenance of a robust inflammatory profile. The induction of this inflammatory state is typically antimicrobial and related to pathogen clearance. However, depending on the infection, STING-mediated immune responses can be detrimental to the host, facilitating bacterial survival, indicating an intricate balance between immune signaling and inflammation during bacterial infections. In this paper, we review recent insights regarding the role of STING in inducing an inflammatory profile upon intracellular bacterial entry in host cells and discuss the impact of STING signaling on the outcome of infection. Unraveling the STING-mediated inflammatory responses can enable a better understanding of the pathogenesis of certain bacterial diseases and reveal the potential of new antimicrobial therapy.

scholarly journals Engineering supramolecular organizing centers for optogenetic control of innate immune responses

2020 ◽  
Author(s):  
Peng Tan ◽  
Lian He ◽  
Yubin Zhou
Keyword(s):  
Transcriptional Activation ◽  
Inflammatory Responses ◽  
Protein Complexes ◽  
Innate Immune ◽  
Type I Interferons ◽  
Type I ◽  
Dependent Manner ◽  
Innate Immune Responses ◽  
Spatiotemporal Resolution ◽  
Oligomeric Protein

AbstractThe spatiotemporal organization of oligomeric protein complexes and translocons, such as the supramolecular organizing centers (SMOC) made of MyDDosome and MAVSome, are essential for transcriptional activation of host inflammatory responses and immune metabolisms. Light-inducible assembly of MyDDosome and MAVSome are presented herein to induce activation of nuclear factor-kB (NF-κB) and type-I interferons (IFNs). Engineering of SMOCs and the downstream transcription factor permits programmable and customized innate immune operations in a light-dependent manner. These synthetic molecular tools will likely enable optical and user-defined modulation of innate immunity at a high spatiotemporal resolution to facilitate mechanistic studies of distinct modes of innate immune activations and potential intervention of immune disorders and cancer.

scholarly journals Type I Interferons in Bacterial Infections: A Balancing Act

2016 ◽  
Vol 7 ◽  
Author(s):  
Pavel Kovarik ◽  
Virginia Castiglia ◽  
Masa Ivin ◽  
Florian Ebner
Keyword(s):  
Bacterial Infections ◽  
Type I Interferons ◽  
Type I

scholarly journals Danger-Associated Molecular Patterns (DAMPs): Molecular Triggers for Sterile Inflammation in the Liver

2018 ◽  
Vol 19 (10) ◽  
pp. 3104 ◽  
Author(s):  
Sabine Mihm
Keyword(s):  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Sterile Inflammation ◽  
Type I Interferons ◽  
Neutrophil Granulocytes ◽  
Type I ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion ◽  
Molecular Patterns

Inflammatory liver diseases in the absence of pathogens such as intoxication by xenobiotics, cholestatic liver injury, hepatic ischemia-reperfusion injury (I/R), non-alcoholic steatohepatitis (NASH), or alcoholic liver disease (ALD) remain threatening conditions demanding specific therapeutic options. Caused by various different noxae, all these conditions have been recognized to be triggered by danger- or death-associated molecular patterns (DAMPs), discompartmentalized self-structures released by dying cells. These endogenous, ectopic molecules comprise proteins, nucleic acids, adenosine triphosphate (ATP), or mitochondrial compounds, among others. This review resumes the respective modes of their release—passively by necrotic hepatocytes or actively by viable or apoptotic parenchymal cells—and their particular roles in sterile liver pathology. It addresses their sensors and the initial inflammatory responses they provoke. It further addresses a resulting second wave of parenchymal death that might be of different mode, boosting the release of additional, second-line DAMPs. Thus, triggering a more complex and pronounced response. Initial and secondary inflammatory responses comprise the activation of Kupffer cells (KCs), the attraction and activation of monocytes and neutrophil granulocytes, and the induction of type I interferons (IFNs) and their effectors. A thorough understanding of pathophysiology is a prerequisite for identifying rational therapeutic targets.

scholarly journals The activation of bystander CD8+ T cells and their roles in viral infection

2019 ◽  
Vol 51 (12) ◽  
pp. 1-9 ◽  
Author(s):  
Tae-Shin Kim ◽  
Eui-Cheol Shin
Keyword(s):  
T Cells ◽  
Viral Infections ◽  
Hepatitis A Virus ◽  
Tissue Injury ◽  
Strong Association ◽  
Killer Cell ◽  
Type I Interferons ◽  
Type I ◽  
Dependent Manner ◽  
Bystander Activation

AbstractDuring viral infections, significant numbers of T cells are activated in a T cell receptor-independent and cytokine-dependent manner, a phenomenon referred to as “bystander activation.” Cytokines, including type I interferons, interleukin-18, and interleukin-15, are the most important factors that induce bystander activation of T cells, each of which plays a somewhat different role. Bystander T cells lack specificity for the pathogen, but can nevertheless impact the course of the immune response to the infection. For example, bystander-activated CD8+ T cells can participate in protective immunity by secreting cytokines, such as interferon-γ. They also mediate host injury by exerting cytotoxicity that is facilitated by natural killer cell-activating receptors, such as NKG2D, and cytolytic molecules, such as granzyme B. Interestingly, it has been recently reported that there is a strong association between the cytolytic function of bystander-activated CD8+ T cells and host tissue injury in patients with acute hepatitis A virus infection. The current review addresses the induction of bystander CD8+ T cells, their effector functions, and their potential roles in immunity to infection, immunopathology, and autoimmunity.

scholarly journals Autophagy Inhibits Grass Carp Reovirus (GCRV) Replication and Protects Ctenopharyngodon idella Kidney (CIK) Cells from Excessive Inflammatory Responses after GCRV Infection

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1296
Author(s):  
Pengfei Chu ◽  
Libo He ◽  
Rong Huang ◽  
Lanjie Liao ◽  
Yongming Li ◽  
...  
Keyword(s):  
Virus Replication ◽  
Grass Carp ◽  
Inflammatory Responses ◽  
Early Stage ◽  
Tracer Tests ◽  
Type I Interferons ◽  
Ctenopharyngodon Idella ◽  
Type I ◽  
Grass Carp Reovirus ◽  
Cik Cells

Autophagy is an essential and highly conserved process in mammals, which is critical to maintaining physiological homeostasis, including cell growth, development, repair, and survival. However, the understanding of autophagy in fish virus replication is limited. In this study, we found that grass carp reovirus (GCRV) infection stimulated autophagy in the spleen of grass carp (Ctenopharyngodon idella). Moreover, both Western blot (WB) analysis and fluorescent tracer tests showed that GCRV infection induced the enhancement of autophagy activation in Ctenopharyngodon idella kidney (CIK) cells. Autophagy inducer rapamycin and autophagy inhibitor 3-MA pretreatment can inhibit and promote the proliferation of GCRV, respectively. In addition, grass carp autophagy-related gene 5 (CiATG5)-induced autophagy, as well as rapamycin, showed effects on GCRV replication in CIK cells. Transcriptome analysis revealed that the total number of differentially expressed genes (DEGs) in CiATG5 overexpression groups was less than that of the control during GCRV infection. Enrichment analysis showed that CiATG5 overexpression induced the enhancement of autophagy, lysosome, phagosome, and apoptosis in the early stage of GCRV infection, which led to the clearance of viruses. In the late stage, steroid biosynthesis, DNA replication, terpenoid backbone biosynthesis, and carbon metabolism were upregulated, which contributed to cell survival. Moreover, signaling pathways involved in the immune response and cell death were downregulated in CiATG5 overexpression groups. Further study showed that CiATG5 repressed the expression of inflammatory response genes, including cytokines and type I interferons. Taken together, the results demonstrate that autophagy represses virus replication and attenuates acute inflammatory responses to protect cells.

scholarly journals Amphiregulin Regulates Phagocytosis-Induced Cell Death in Monocytes via EGFR and the Bcl-2 Protein Family

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Christopher Platen ◽  
Stephan Dreschers ◽  
Jessica Wappler ◽  
Andreas Ludwig ◽  
Stefan Düsterhöft ◽  
...  
Keyword(s):  
Cell Death ◽  
Bacterial Infections ◽  
Caspase 3 ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Dependent Manner ◽  
Intrinsic Apoptosis ◽  
Caspase 9 ◽  
Apoptosis Pathway ◽  
Intrinsic Apoptosis Pathway

Neonates are extremely susceptible to bacterial infections, and evidences suggest that phagocytosis-induced cell death (PICD) is less frequently triggered in neonatal monocytes than in monocytes from adult donors. An insufficient termination of the inflammatory response, leading to a prolonged survival of neonatal monocytes with ongoing proinflammatory cytokine release, could be associated with the progression of various inflammatory diseases in neonates. Our previous data indicate that amphiregulin (AREG) is increasingly expressed on the cell surface of neonatal monocytes, resulting in remarkably higher soluble AREG levels after proteolytic shedding. In this study, we found that E. coli-infected neonatal monocytes show an increased phosphorylation of ERK, increased expression of Bcl-2 and Bcl-XL, and reduced levels of cleaved caspase-3 and caspase-9 compared to adult monocytes. In both cell types, additional stimulation with soluble AREG further increased ERK activation and expression of Bcl-2 and Bcl-XL and reduced levels of cleaved caspase-3 and caspase-9 in an EGFR-dependent manner. These data suggest that reduced PICD of neonatal monocytes could be due to reduced intrinsic apoptosis and that AREG can promote protection against PICD. This reduction of the intrinsic apoptosis pathway in neonatal monocytes could be relevant for severely prolonged inflammatory responses of neonates.

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