Multifunctional Antibiotic–Host Defense Peptide Conjugate Kills Bacteria, Eradicates Biofilms, and Modulates the Innate Immune Response

2021 ◽  
Author(s):  
Hashem Etayash ◽  
Morgan Alford ◽  
Noushin Akhoundsadegh ◽  
Matthew Drayton ◽  
Suzana K. Straus ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Host Defense ◽  
Innate Immune ◽  
Host Defense Peptide

scholarly journals Interaction and Cellular Localization of the Human Host Defense Peptide LL-37 with Lung Epithelial Cells

2005 ◽  
Vol 73 (1) ◽  
pp. 583-591 ◽  
Author(s):  
Y. Elaine Lau ◽  
Annett Rozek ◽  
Monisha G. Scott ◽  
Danika L. Goosney ◽  
Donald J. Davidson ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Innate Immune Response ◽  
Host Defense ◽  
Cellular Localization ◽  
Innate Immune ◽  
Lung Epithelial Cells ◽  
Perinuclear Region ◽  
Effector Cells ◽  
Host Defense Peptide

ABSTRACT LL-37 is a human cationic host defense peptide that is an essential component of innate immunity. In addition to its modest antimicrobial activity, LL-37 affects the gene expression and behavior of effector cells involved in the innate immune response, although its mode of interaction with eukaryotic cells remains unclear. The interaction of LL-37 with epithelial cells was characterized in tissue culture by using biotinylated LL-37 and confocal microscopy. It was demonstrated that LL-37 was actively taken up into A549 epithelial cells and eventually localized to the perinuclear region. Specific inhibitors were used to demonstrate that the uptake process was not mediated by actin but required elements normally involved in endocytosis and that trafficking to the perinuclear region was dependent on microtubules. By using nonlinear regression analysis, it was revealed that A549 epithelial cells have two receptors for LL-37B, with high and low affinity for LL-37, respectively. These results indicate the mode of interaction of LL-37 with epithelial cells and further our understanding of its role in modulating the innate immune response.

Innate Immune Response to Cytoplasmic DNA: Mechanisms and Diseases

2020 ◽  
Vol 38 (1) ◽  
pp. 79-98 ◽  
Author(s):  
Ming-Ming Hu ◽  
Hong-Bing Shu
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Host Defense ◽  
Cyclic Gmp ◽  
Molecular Mechanisms ◽  
Adaptor Protein ◽  
Innate Immune ◽  
Cellular Stress Response ◽  
Cytoplasmic Dna ◽  
Stress Response Pathway

DNA has been known to be a potent immune stimulus for more than half a century. However, the underlying molecular mechanisms of DNA-triggered immune response have remained elusive until recent years. Cyclic GMP-AMP synthase (cGAS) is a major cytoplasmic DNA sensor in various types of cells that detect either invaded foreign DNA or aberrantly located self-DNA. Upon sensing of DNA, cGAS catalyzes the formation of cyclic GMP-AMP (cGAMP), which in turn activates the ER-localized adaptor protein MITA (also named STING) to elicit the innate immune response. The cGAS-MITA axis not only plays a central role in host defense against pathogen-derived DNA but also acts as a cellular stress response pathway by sensing aberrantly located self-DNA, which is linked to the pathogenesis of various human diseases. In this review, we summarize the spatial and temporal mechanisms of host defense to cytoplasmic DNA mediated by the cGAS-MITA axis and discuss the association of malfunctions of this axis with autoimmune and other diseases.

ROLE OF HOST DEFENSE PEPTIDES OF THE INNATE IMMUNE RESPONSE IN SEPSIS

Shock ◽  
2007 ◽  
pp. 1 ◽  
Author(s):  
Tobias Hirsch ◽  
Marie Metzig ◽  
Andreas Niederbichler ◽  
Hans-Ulrich Steinau ◽  
Elof Eriksson ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Host Defense ◽  
Innate Immune ◽  
Host Defense Peptides ◽  
Defense Peptides

scholarly journals The role of host miRNAs on Mycobacterium tuberculosis

ExRNA ◽  
2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Ava Behrouzi ◽  
Marjan Alimohammadi ◽  
Amir Hossein Nafari ◽  
Mohammad Hadi Yousefi ◽  
Farhad Riazi Rad ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Innate Immune Response ◽  
Host Defense ◽  
Pathogenic Bacteria ◽  
Biological Pathways ◽  
Innate Immune ◽  
The Other ◽  
Non Coding Rnas

Abstract MicroRNAs are non-coding RNAs, playing an important role in regulating many biological pathways, such as innate immune response against various infections. Different studies confirm that many miRNAs act as important regulators in developing a strategy for the survival of Mycobacterium tuberculosis in the host cell. On the other hand, an innate immune response is one of the important aspects of host defense against Mycobacterium. Considering the importance of miRNAs during tuberculosis infection, we focused on studies that performed on the role of various miRNAs related to pathogenic bacteria, M. tuberculosis in the host. Also, we have introduced important miRNAs that can be used as a biomarker for the detection of Mycobacterium.

scholarly journals Host Defense Peptides as Effector Molecules of the Innate Immune Response: A Sledgehammer for Drug Resistance?

2009 ◽  
Vol 10 (9) ◽  
pp. 3951-3970 ◽  
Author(s):  
Lars Steinstraesser ◽  
Ursula Kraneburg ◽  
Tobias Hirsch ◽  
Marco Kesting ◽  
Hans-Ulrich Steinau ◽  
...  
Keyword(s):  
Immune Response ◽  
Drug Resistance ◽  
Innate Immune Response ◽  
Host Defense ◽  
Innate Immune ◽  
Host Defense Peptides ◽  
Effector Molecules ◽  
Defense Peptides

In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days

Blood ◽  
2010 ◽  
Vol 116 (4) ◽  
pp. 625-627 ◽  
Author(s):  
Janesh Pillay ◽  
Ineke den Braber ◽  
Nienke Vrisekoop ◽  
Lydia M. Kwast ◽  
Rob J. de Boer ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Host Defense ◽  
Ex Vivo ◽  
Innate Immune ◽  
Effector Cells ◽  
Short Lifespan ◽  
In Vivo Labeling ◽  
Health And Disease

Abstract Neutrophils are essential effector cells of the innate immune response and are indispensable for host defense. Apart from their antimicrobial functions, neutrophils inform and shape subsequent immunity. This immune modulatory functionality might however be considered limited because of their generally accepted short lifespan (< 1 day). In contrast to the previously reported short lifespans acquired by ex vivo labeling or manipulation, we show that in vivo labeling in humans with the use of 2H2O under homeostatic conditions showed an average circulatory neutrophil lifespan of 5.4 days. This lifespan is at least 10 times longer than previously reported and might lead to reappraisal of novel neutrophil functions in health and disease.

scholarly journals Role of Dendritic Cells and Alveolar Macrophages in Regulating Early Host Defense against Pulmonary Infection with Cryptococcus neoformans

2009 ◽  
Vol 77 (9) ◽  
pp. 3749-3758 ◽  
Author(s):  
John J. Osterholzer ◽  
Jami E. Milam ◽  
Gwo-Hsiao Chen ◽  
Galen B. Toews ◽  
Gary B. Huffnagle ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Cryptococcus Neoformans ◽  
Innate Immune Response ◽  
Host Defense ◽  
Alveolar Macrophages ◽  
Pulmonary Infection ◽  
Innate Immune ◽  
Cellular Mechanisms

ABSTRACT Successful pulmonary clearance of the encapsulated yeast Cryptococcus neoformans requires a T1 adaptive immune response. This response takes up to 3 weeks to fully develop. The role of the initial, innate immune response against the organism is uncertain. In this study, an established model of diphtheria toxin-mediated depletion of resident pulmonary dendritic cells (DC) and alveolar macrophages (AM) was used to assess the contribution of these cells to the initial host response against cryptococcal infection. The results demonstrate that depletion of DC and AM one day prior to infection results in rapid clinical deterioration and death of mice within 6 days postinfection; this effect was not observed in infected groups of control mice not depleted of DC and AM. Depletion did not alter the microbial burden or total leukocyte recruitment in the lung. Mortality (in mice depleted of DC and AM) was associated with increased neutrophil and B-cell accumulation accompanied by histopathologic evidence of suppurative neutrophilic bronchopneumonia, cyst formation, and alveolar damage. Collectively, these data define an important role for DC and AM in regulating the initial innate immune response following pulmonary infection with C. neoformans. These findings provide important insight into the cellular mechanisms which coordinate early host defense against an invasive fungal pathogen in the lung.

Oral Immune Activation by Disgust and Disease-Related Pictures

2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Negative Control ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Markers ◽  
Before And After ◽  
Secondary Analyses ◽  
Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

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