Faculty Opinions recommendation of CXCL5 regulates chemokine scavenging and pulmonary host defense to bacterial infection.

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.

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Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) Plays An Essential Role In Host Defense Against Bacterial Infection In The Lungs

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a3280 ◽

2012 ◽

Author(s):

Ryosuke Kusano ◽

Sui Lin ◽

Yan Ma ◽

John M. Shannon ◽

Henry T. Akinbi

Keyword(s):

Bacterial Infection ◽

Aryl Hydrocarbon Receptor ◽

Host Defense ◽

Essential Role ◽

Aryl Hydrocarbon

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

10.1101/2021.06.09.447810 ◽

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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Cardiac dysfunction induced by experimental myocardial infarction impairs the host defense response to bacterial infection in mice because of reduced phagocytosis of Kupffer cells

Journal of Thoracic and Cardiovascular Surgery ◽

10.1016/j.jtcvs.2009.11.005 ◽

2010 ◽

Vol 140 (3) ◽

pp. 624-632.e3 ◽

Cited By ~ 4

Author(s):

Yashiro Nogami ◽

Manabu Kinoshita ◽

Bonpei Takase ◽

Akihito Inatsu ◽

Masayuki Ishihara ◽

...

Keyword(s):

Myocardial Infarction ◽

Bacterial Infection ◽

Host Defense ◽

Kupffer Cells ◽

Defense Response ◽

Cardiac Dysfunction ◽

Experimental Myocardial Infarction ◽

Host Defense Response

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

Scientific Reports ◽

10.1038/srep31936 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 13

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.

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Role of copper in defending against bacterial infection

10.32469/10355/47147 ◽

2015 ◽

Author(s):

◽

Erik Ladomersky

Keyword(s):

Bacterial Infection ◽

Host Defense ◽

Immune Defense ◽

Copper Proteins ◽

University Of Missouri ◽

Susceptibility To Infection ◽

Essential Nutrient ◽

The University ◽

The Relationship

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Copper is an essential nutrient. It plays an important role in development, pigmentation, neurological function, and immune defense. Copper deficiency is known to make host's more susceptible to infection. In this work we show that two copper proteins, ATP7A and ceruloplasmin, are important for host defense against bacterial infection. Studies have shown ATP7A is responsible for increasing copper concentrations inside the phagosome. Our study sheds light on the role of Atp7a and copper in adaptive immunity, and provide a biochemical model for understanding the relationship between copper malnutrition and susceptibility to infection. Iron, another essential nutrient, is linked with copper through the actions of copper-dependent proteins which play a role in maintaining normal iron levels in the blood. One of these proteins is ceruloplasmin, a protein that is also upregulated during infection. Our study sheds light onto why this protein is necessary for host defense against Salmonella infection.

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Roles of a Mast Cell–Specific Receptor MRGPRX2 in Host Defense and Inflammation

Journal of Dental Research ◽

10.1177/0022034520919107 ◽

2020 ◽

Vol 99 (8) ◽

pp. 882-890 ◽

Cited By ~ 1

Author(s):

C. Chompunud Na Ayudhya ◽

S. Roy ◽

M. Thapaliya ◽

H. Ali

Keyword(s):

Mast Cells ◽

Bacterial Infection ◽

Host Defense ◽

Immune Cells ◽

Inflammatory Pain ◽

Bacterial Infections ◽

Neurogenic Inflammation ◽

Inflammatory Diseases ◽

Adaptive Immune Cells ◽

Novel Approaches

Mast cells are multifunctional immune cells that are found most abundantly at host-environment interfaces, such as the skin, respiratory tract, and oral/gastrointestinal mucosa. Not surprisingly, mast cells act as sentinel cells that sense microbial attacks and initiate a protective immune response and promote healing. Although mast cells share many features with other innate immune effector cells, such as neutrophils and macrophages, they uniquely interact closely with blood vessels and release an extensive set of mediators for the recruitment of innate and adaptive immune cells. A novel human G protein-coupled receptor (GPCR), known as Mas-related GPCR-X2 (MRGPRX2, mouse ortholog, MrgprB2), has recently been identified, which is expressed on mast cells but not neutrophils and macrophages. Interestingly, activation of MrgprB2 by bacteria-derived quorum-sensing peptides inhibits bacterial growth, prevents biofilm formation, and leads to the recruitment of neutrophils to effectively clear bacteria. Furthermore, host defense antimicrobial peptides and small-molecule peptide mimetics also activate mast cells via MRGPRX2/B2. MrgprB2-mediated activation of local mast cells also clears cutaneous bacterial infection, promotes healing, and protects against reinfection. In addition to their role in host defense, mast cells contribute to a number of chronic inflammatory diseases such as periodontitis, neurogenic inflammation, and inflammatory pain likely via the activation of MRGPRX2. In this review, we discuss the roles of MRGPRX2/B2 in the clearance of bacterial infection, wound healing, periodontal disease, neurogenic inflammation, and inflammatory pain. We propose that harnessing mast cells’ host defense and immunomodulatory properties via the activation of MRGPRX2 may lead to novel approaches for the treatment of drug-resistant bacterial infections. On the other hand, increased MRGPRX2 expression on mast cells and their inappropriate activation may contribute to periodontitis, neurogenic inflammation, and inflammatory pain. Thus, targeting MRGPRX2 could provide novel approaches to modulate these conditions.

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

Journal of Experimental Medicine ◽

10.1084/jem.20182031 ◽

2019 ◽

Vol 216 (3) ◽

pp. 482-500 ◽

Cited By ~ 29

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.

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