scholarly journals Host Defense against Bacterial Infection and Bacterial Toxin-induced Impairment of Innate Immunity

2018 ◽  
Vol 138 (10) ◽  
pp. 1249-1253 ◽  
Author(s):  
Masaya Takehara
Keyword(s):  
Innate Immunity ◽  
Bacterial Infection ◽  
Host Defense ◽  
Bacterial Toxin

scholarly journals Pregnane X Receptor Regulates Pathogen-Induced Inflammation and Host Defense against an Intracellular Bacterial Infection through Toll-like Receptor 4

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhijuan Qiu ◽  
Jorge L. Cervantes ◽  
Basak B. Cicek ◽  
Subhajit Mukherjee ◽  
Madhukumar Venkatesh ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Bacterial Infection ◽  
Host Defense ◽  
Negative Impact ◽  
Pregnane X Receptor ◽  
Negative Regulator ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Chemokine Production ◽  
Inflammatory Monocytes

Abstract The nuclear pregnane X receptor (PXR) plays a central role in regulating xenobiotic metabolism. We now report a novel role for PXR as a critical negative regulator of innate immunity after infection. Pxr −/− mice exhibited remarkably elevated pro-inflammatory cytokine and chemokine production following infection with Listeria monocytogenes (Lm). Despite the more robust innate immune response, Pxr −/− mice were highly susceptible to Lm infection. Surprisingly, disruption of the Toll-like receptor 4 (TLR4) but not TLR2 signaling restored the inflammation to normal levels and the ability to clear Lm in Pxr −/− mice. Mechanistically, the heightened inflammation in Pxr −/− mice resulted in the death of inflammatory monocytes that led to the enhanced susceptibility to Lm infection. These data demonstrated that PXR regulated pathogen-induced inflammation and host defense against Lm infection through modulating the TLR4 pathway. In summary, we discovered an apical role for PXR in regulating innate immunity. In addition, we uncovered a remarkable negative impact of the TLR4 pathway in controlling the quality of the inflammatory response and host defense against a gram-positive bacterial infection.

scholarly journals Interferon-induced guanylate-binding proteins: Guardians of host defense in health and disease

2019 ◽  
Vol 216 (3) ◽  
pp. 482-500 ◽  
Author(s):  
Kyle Tretina ◽  
Eui-Soon Park ◽  
Agnieszka Maminska ◽  
John D. MacMicking
Keyword(s):  
Innate Immunity ◽  
Bacterial Infection ◽  
Host Defense ◽  
Tissue Damage ◽  
Binding Proteins ◽  
Wide Spectrum ◽  
Cell Types ◽  
Microbial Pathogens ◽  
Health And Disease ◽  
Basic Biology

Guanylate-binding proteins (GBPs) have recently emerged as central orchestrators of immunity to infection, inflammation, and neoplastic diseases. Within numerous host cell types, these IFN-induced GTPases assemble into large nanomachines that execute distinct host defense activities against a wide variety of microbial pathogens. In addition, GBPs customize inflammasome responses to bacterial infection and sepsis, where they act as critical rheostats to amplify innate immunity and regulate tissue damage. Similar functions are becoming evident for metabolic inflammatory syndromes and cancer, further underscoring the importance of GBPs within infectious as well as altered homeostatic settings. A better understanding of the basic biology of these IFN-induced GTPases could thus benefit clinical approaches to a wide spectrum of important human diseases.

scholarly journals Mitofusin-2 boosts innate immunity through the maintenance of aerobic glycolysis and activation of xenophagy in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Prashanta Silwal ◽  
Jin Kyung Kim ◽  
Sang Min Jeon ◽  
June-Young Lee ◽  
Young Jae Kim ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Bacterial Infection ◽  
Host Defense ◽  
Inflammatory Responses ◽  
Aerobic Glycolysis ◽  
Hypoxia Inducible Factor ◽  
Chain Complex ◽  
Mitochondrial Respiratory Chain ◽  
Mitofusin 2 ◽  
Mitochondrial Respiratory Chain Complex

AbstractMitochondrial function and innate immunity are intimately linked; however, the mechanisms how mitochondrion-shaping proteins regulate innate host defense remains largely unknown. Herein we show that mitofusin-2 (MFN2), a mitochondrial fusion protein, promotes innate host defense through the maintenance of aerobic glycolysis and xenophagy via hypoxia-inducible factor (HIF)-1α during intracellular bacterial infection. Myeloid-specific MFN2 deficiency in mice impaired the antimicrobial and inflammatory responses against mycobacterial and listerial infection. Mechanistically, MFN2 was required for the enhancement of inflammatory signaling through optimal induction of aerobic glycolysis via HIF-1α, which is activated by mitochondrial respiratory chain complex I and reactive oxygen species, in macrophages. MFN2 did not impact mitophagy during infection; however, it promoted xenophagy activation through HIF-1α. In addition, MFN2 interacted with the late endosomal protein Rab7, to facilitate xenophagy during mycobacterial infection. Our findings reveal the mechanistic regulations by which MFN2 tailors the innate host defense through coordinated control of immunometabolism and xenophagy via HIF-1α during bacterial infection.

scholarly journals TOR functions as a molecular switch connecting an iron cue with host innate defense against bacterial infection

PLoS Genetics ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. e1009383
Author(s):  
Yi-Cheng Ma ◽  
Li-Li Dai ◽  
Bei-Bei Qiu ◽  
Ying Zhou ◽  
Yu-Qiang Zhao ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Bacterial Infection ◽  
Host Defense ◽  
Bacterial Infections ◽  
Iron Availability ◽  
Innate Defense ◽  
Iron Sequestration ◽  
Serovar Typhimurium ◽  
Important Regulator ◽  
Host Innate Immunity

As both host and pathogen require iron for survival, iron is an important regulator of host-pathogen interactions. However, the molecular mechanism by which how the availability of iron modulates host innate immunity against bacterial infections remains largely unknown. Using the metazoan Caenorhabditis elegans as a model, we demonstrate that infection with a pathogenic bacterium Salmonella enterica serovar Typhimurium induces autophagy by inactivating the target of rapamycin (TOR). Although the transcripts of ftn-1 and ftn-2 encoding two H-ferritin subunits are upregulated upon S. Typhimurium infection, the ferritin protein is kept at a low level due to its degradation mediated by autophagy. Autophagy, but not ferritin, is required for defense against S. Typhimurium infection under normal circumstances. Increased abundance of iron suppresses autophagy by activating TOR, leading to an increase in the ferritin protein level. Iron sequestration, but not autophagy, becomes pivotal to protect the host from S. Typhimurium infection in the presence of exogenous iron. Our results show that TOR acts as a regulator linking iron availability with host defense against bacterial infection.

scholarly journals Effectors Targeting the Unfolded Protein Response during Intracellular Bacterial Infection

2021 ◽  
Vol 9 (4) ◽  
pp. 705
Author(s):  
Manal H. Alshareef ◽  
Elizabeth L. Hartland ◽  
Kathleen McCaffrey
Keyword(s):  
Bacterial Infection ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Host Defense ◽  
Effector Proteins ◽  
Dual Nature ◽  
Unfolded Protein ◽  
Bacterial Replication ◽  
The Unfolded Protein Response ◽  
Protein Response

The unfolded protein response (UPR) is a homeostatic response to endoplasmic reticulum (ER) stress within eukaryotic cells. The UPR initiates transcriptional and post-transcriptional programs to resolve ER stress; or, if ER stress is severe or prolonged, initiates apoptosis. ER stress is a common feature of bacterial infection although the role of the UPR in host defense is only beginning to be understood. While the UPR is important for host defense against pore-forming toxins produced by some bacteria, other bacterial effector proteins hijack the UPR through the activity of translocated effector proteins that facilitate intracellular survival and proliferation. UPR-mediated apoptosis can limit bacterial replication but also often contributes to tissue damage and disease. Here, we discuss the dual nature of the UPR during infection and the implications of UPR activation or inhibition for inflammation and immunity as illustrated by different bacterial pathogens.

Thromboinflammation as a Driver of Venous Thromboembolism

2021 ◽  
Vol 41 (06) ◽  
pp. 428-432
Author(s):  
Nadine Gauchel ◽  
Krystin Krauel ◽  
Muataz Ali Hamad ◽  
Christoph Bode ◽  
Daniel Duerschmied
Keyword(s):  
Innate Immunity ◽  
Venous Thromboembolism ◽  
Host Defense ◽  
Thrombus Formation ◽  
Pathological Process ◽  
Defense Systems ◽  
Underlying Mechanisms

AbstractThrombus formation has been identified as an integral part in innate immunity, termed immunothrombosis. Activation of host defense systems is known to result in a procoagulant environment. In this system, cellular players as well as soluble mediators interact with each other and their dysregulation can lead to the pathological process of thromboinflammation. These mechanisms have been under intensified investigation during the COVID-19 pandemic. In this review, we focus on the underlying mechanisms leading to thromboinflammation as one trigger of venous thromboembolism.

scholarly journals Megakaryocyte derived immune-stimulating cells regulate host-defense immunity against bacterial pathogens

2021 ◽  
Author(s):  
Jin Wang ◽  
Jiayi Xie ◽  
Xue Han ◽  
Daosong Wang ◽  
Minqi Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Bacterial Infection ◽  
Host Defense ◽  
T Cell Activation ◽  
Cell Activation ◽  
Hematopoietic Stem ◽  
Bacterial Response ◽  
Stem Cell Quiescence ◽  
Express Cell

Megakaryocytes (MKs) continuously produce platelets in bone marrow to support hemostasis. However, MKs also play roles beyond thrombopoiesis as they regulate hematopoietic stem cell quiescence and erythropoiesis, which suggests the functional heterogeneity of MKs. Here, using single-cell sequencing we identified an MK-derived immune-stimulating cell (MDIC) population, which plays an important role in host-protective response against bacteria. In contrast to platelet-generating MKs, MDICs highly express cell migration, immune-modulatory, and response genes. Upon Listeria (L.) monocytogenes infection, MDICs egress to circulation and infiltrate into the spleen, liver and lung. MDICs interact with myeloid cells to promote their migration and tissue infiltration. More importantly, MDICs stimulate phagocytosis of macrophages and neutrophils by producing TNFα and IL-6 and facilitating antigen-specific T cell activation via IL-6 to enhance anti-bacterial response. Ablation of MKs reduced innate immune response and compromised T cell activation in spleen and liver, impairs the anti-bacterial effects in mice under L. monocytogenes challenge. Finally, infection-induced emergency megakaryopoiesis efficiently stimulated MDICs generation upon bacterial infection. Overall, we identify MDICs as a novel MK subpopulation, which regulates host-defense immune response against bacterial infection.

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