scholarly journals Host Defense Peptides in the Oral Cavity and the Lung: Similarities and Differences

2008 ◽  
Vol 87 (10) ◽  
pp. 915-927 ◽  
Author(s):  
G. Diamond ◽  
N. Beckloff ◽  
L.K. Ryan
Keyword(s):  
Oral Cavity ◽  
Host Defense ◽  
Gingival Crevicular Fluid ◽  
Immune Defense ◽  
The Body ◽  
Microbial Colonization ◽  
Host Defense Peptides ◽  
Innate Defense ◽  
Defense Peptides

Peptides with broad-spectrum antimicrobial activity are found in the mucosal surfaces at many sites in the body, including the airway, the oral cavity, and the digestive tract. Based on their in vitro antimicrobial and other immunomodulatory activities, these host defense peptides have been proposed to play an important role in the innate defense against pathogenic microbial colonization. The genes that encode these peptides are up-regulated by pathogens, further supporting their role in innate immune defense. However, the differences in the local microbial environments between the generally sterile airway and the highly colonized oral cavity suggest a more complex role for these peptides in innate immunity. For example, β-defensin genes are induced in the airway by all bacteria and Toll-like receptor (TLR) agonists primarily through an NF-κB-mediated pathway. In contrast, the same genes are induced in the gingival epithelium by only a subset of bacteria and TLR ligands, via different pathways. Furthermore, the environments into which the peptides are secreted—specifically saliva, gingival crevicular fluid, and airway surface fluid—differ greatly and can effect their respective activities in host defense. In this review, we examine the differences and similarities between host defense peptides in the oral cavity and the airway, to gain a better understanding of their contributions to immunity.

scholarly journals Mechanistic Fingerprinting Reveals Kinetic Signatures of Resistance to Daptomycin and Host Defense Peptides in Streptococcus mitis-oralis

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 404
Author(s):  
Michael R. Yeaman ◽  
Liana C. Chan ◽  
Nagendra N. Mishra ◽  
Arnold S. Bayer
Keyword(s):  
Flow Cytometry ◽  
Host Defense ◽  
Durable Resistance ◽  
Cross Resistance ◽  
Streptococcus Mitis ◽  
Host Defense Peptides ◽  
Strain Pair ◽  
Defense Peptides

Streptococcus mitis-oralis (S. mitis-oralis) infections are increasingly prevalent in specific populations, including neutropenic cancer and endocarditis patients. S. mitis-oralis strains have a propensity to evolve rapid, high-level and durable resistance to daptomycin (DAP-R) in vitro and in vivo, although the mechanism(s) involved remain incompletely defined. We examined mechanisms of DAP-R versus cross-resistance to cationic host defense peptides (HDPs), using an isogenic S. mitis-oralis strain-pair: (i) DAP-susceptible (DAP-S) parental 351-WT (DAP MIC = 0.5 µg/mL), and its (ii) DAP-R variant 351-D10 (DAP MIC > 256 µg/mL). DAP binding was quantified by flow cytometry, in-parallel with temporal (1–4 h) killing by either DAP or comparative prototypic cationic HDPs (hNP-1; LL-37). Multicolor flow cytometry was used to determine kinetic cell responses associated with resistance or susceptibility to these molecules. While overall DAP binding was similar between strains, a significant subpopulation of 351-D10 cells hyper-accumulated DAP (>2–4-fold vs. 351-WT). Further, both DAP and hNP-1 induced cell membrane (CM) hyper-polarization in 351-WT, corresponding to significantly greater temporal DAP-killing (vs. 351-D10). No strain-specific differences in CM permeabilization, lipid turnover or regulated cell death were observed post-exposure to DAP, hNP-1 or LL-37. Thus, the adaptive energetics of the CM appear coupled to the outcomes of interactions of S. mitis-oralis with DAP and selected HDPs. In contrast, altered CM permeabilization, proposed as a major mechanism of action of both DAP and HDPs, did not differentiate DAP-S vs. DAP-R phenotypes in this S. mitis-oralis strain-pair.

Inhalation Delivery of Host Defense Peptides (HDP) using Nano- Formulation Strategies: A Pragmatic Approach for Therapy of Pulmonary Ailments

2020 ◽  
Vol 21 (4) ◽  
pp. 369-378 ◽  
Author(s):  
Suneera Adlakha ◽  
Ankur Sharma ◽  
Kalpesh Vaghasiya ◽  
Eupa Ray ◽  
Rahul Kumar Verma
Keyword(s):  
Host Defense ◽  
Respiratory Infections ◽  
Drug Regimen ◽  
The Body ◽  
Host Defense Peptides ◽  
Suitable Alternative ◽  
Inhalation Delivery ◽  
Defense Peptides ◽  
Nano Formulation ◽  
Pass Metabolism

Host defense peptides (HDP) are small cationic molecules released by the immune systems of the body, having multidimensional properties including anti-inflammatory, anticancer, antimicrobial and immune-modulatory activity. These molecules gained importance due to their broad-spectrum pharmacological activities, and hence being actively investigated. Presently, respiratory infections represent a major global health problem, and HDP has an enormous potential to be used as an alternative therapeutics against respiratory infections and related inflammatory ailments. Because of their short half-life, protease sensitivity, poor pharmacokinetics, and first-pass metabolism, it is challenging to deliver HDP as such inside the physiological system in a controlled way by conventional delivery systems. Many HDPs are efficacious only at practically high molar-concentrations, which is not convincing for the development of drug regimen due to their intrinsic detrimental effects. To avail the efficacy of HDP in pulmonary diseases, it is essential to deliver an appropriate payload into the targeted site of lungs. Inhalable HDP can be a potentially suitable alternative for various lung disorders including tuberculosis, Cystic fibrosis, Pneumonia, Lung cancer, and others as they are active against resistant microbes and cells and exhibit improved targeting with reduced adverse effects. In this review, we give an overview of the pharmacological efficacy of HDP and deliberate strategies for designing inhalable formulations for enhanced activity and issues related to their clinical implications.

scholarly journals Inorganic Chemistry of Defensive Peroxidases in the Human Oral Cavity

2008 ◽  
Vol 87 (10) ◽  
pp. 900-914 ◽  
Author(s):  
M. T. Ashby
Keyword(s):  
Inorganic Chemistry ◽  
Oral Cavity ◽  
Host Response ◽  
Gingival Crevicular Fluid ◽  
In Vivo Studies ◽  
Oral Diseases ◽  
Microbial Infection ◽  
Innate Defense ◽  
Inorganic Species

The innate host response system is comprised of various mechanisms for orchestrating host response to microbial infection of the oral cavity. The heterogeneity of the oral cavity and the associated microenvironments that are produced give rise to different chemistries that affect the innate defense system. One focus of this review is on how these spatial differences influence the two major defensive peroxidases of the oral cavity, salivary peroxidase (SPO) and myeloperoxidase (MPO). With hydrogen peroxide (H2O2) as an oxidant, the defensive peroxidases use inorganic ions to produce antimicrobials that are generally more effective than H2O2 itself. The concentrations of the inorganic substrates are different in saliva vs. gingival crevicular fluid (GCF). Thus, in the supragingival regime, SPO and MPO work in unison for the exclusive production of hypothiocyanite (OSCN−, a reactive inorganic species), which constantly bathes nascent plaques. In contrast, MPO is introduced to the GCF during inflammatory response, and in that environment it is capable of producing hypochlorite (OCl−), a chemically more powerful oxidant that is implicated in host tissue damage. A second focus of this review is on inter-person variation that may contribute to different peroxidase function. Many of these differences are attributed to dietary or smoking practices that alter the concentrations of relevant inorganic species in the oral cavity ( e.g.: fluoride, F−; cyanide, CN−; cyanate, OCN−; thiocyanate, SCN−; and nitrate, NO3−). Because of the complexity of the host and microflora biology and the associated chemistry, it is difficult to establish the significance of the human peroxidase systems during the pathogenesis of oral diseases. The problem is particularly complex with respect to the gingival sulcus and periodontal pockets (where the very different defensive stratagems of GCF and saliva co-mingle). Despite this complexity, intriguing in vitro and in vivo studies are reviewed here that reveal the interplay between peroxidase function and associated inorganic chemistry.

scholarly journals Host defense peptides clavanins A and MO reduce in vitro osteoclastogenesis

2021 ◽  
Vol 20 ◽  
pp. e211512
Author(s):  
Ingrid Aquino Amorim ◽  
Stella Maris de Freitas Lima ◽  
Ana Paula de Castro Cantuária ◽  
Mirna de Souza Freire ◽  
Jeeser Alves de Almeida ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bone Resorption ◽  
Calcium Hydroxide ◽  
Host Defense ◽  
Nitric Oxide Production ◽  
Cellular Viability ◽  
Host Defense Peptides ◽  
Oxide Production ◽  
Defense Peptides

Aim: Several systemic diseases, such as periodontitis and apical periodontitis, can cause extensive bone resorption. Host defense peptides may have the potential for the development of novel therapies for the bone resorption process. This study evaluated the potential of host defense peptides clavanins A, MO, and LL-37 in in vitro osteoclastogenesis. Methods: RAW 264.7 cultures were stimulated with recombinant of receptor activator of nuclear factor kappa B ligand in the presence of different tested concentrations of host defense peptides, besides calcium hydroxide and doxycycline. Cellular viability, nitric oxide production, and a number of differentiated osteoclast-like cells were also evaluated. Results: Results showed that none of the substances were cytotoxic, except for 128 μg.mL-1 of doxycycline after 3 days. Host defense peptides, calcium hydroxide, and doxycycline did not interfere in nitric oxide production or downregulated it. An exception was observed in the presence of 2 μg.mL-1 of doxycycline, in which nitric oxide production was up-regulated. All host defense peptides were capable of reducing osteoclast-like cell differentiation. Conclusion: Host defense peptides clavanins A and MO demonstrated to be potential suppressors of osteoclastogenesis in vitro without interfering in cellular viability and nitric oxide production. These promising results need to be further analyzed in in vivo models of bone resorption.

scholarly journals The Host Defense Peptide Beta-Defensin 1 Confers Protection against Bordetella pertussis in Newborn Piglets

2006 ◽  
Vol 74 (4) ◽  
pp. 2338-2352 ◽  
Author(s):  
Shokrollah Elahi ◽  
Rachelle M. Buchanan ◽  
Sam Attah-Poku ◽  
Hugh G. G. Townsend ◽  
Lorne A. Babiuk ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Host Defense ◽  
Bordetella Pertussis ◽  
Respiratory Infections ◽  
Upper Respiratory Tract ◽  
Host Defense Peptides ◽  
Newborn Piglets ◽  
Defense Peptides

ABSTRACT Innate immunity plays an important role in protection against respiratory infections in humans and animals. Host defense peptides such as beta-defensins represent major components of innate immunity. We recently developed a novel porcine model of pertussis, an important respiratory disease of young children and infants worldwide. Here, we investigated the role of porcine beta-defensin 1 (pBD-1), a porcine defensin homologue of human beta-defensin 2, in conferring protection against respiratory infection with Bordetella pertussis. In this model, newborn piglets were fully susceptible to infection and developed severe bronchopneumonia. In contrast, piglets older than 4 weeks of age were protected against infection with B. pertussis. Protection was associated with the expression of pBD-1 in the upper respiratory tract. In fact, pBD-1 expression was developmentally regulated, and the absence of pBD-1 was thought to contribute to the increased susceptibility of newborn piglets to infection with B. pertussis. Bronchoalveolar lavage specimens collected from older animals as well as chemically synthesized pBD-1 displayed strong antimicrobial activity against B. pertussis in vitro. Furthermore, in vivo treatment of newborn piglets with only 500 μg pBD-1 at the time of challenge conferred protection against infection with B. pertussis. Interestingly, pBD-1 displayed no bactericidal activity in vitro against Bordetella bronchiseptica, a closely related natural pathogen of pigs. Our results demonstrate that host defense peptides play an important role in protection against pertussis and are essential in modulating innate immune responses against respiratory infections.

Antiviral Activities of Human Host Defense Peptides

2020 ◽  
Vol 27 (9) ◽  
pp. 1420-1443 ◽  
Author(s):  
David C. Brice ◽  
Gill Diamond
Keyword(s):  
Host Defense ◽  
Broad Spectrum ◽  
Structural Features ◽  
Host Defense Peptides ◽  
Enveloped Viruses ◽  
Human Host ◽  
Wide Range ◽  
Defense Peptides

Peptides with broad-spectrum antimicrobial activity are found widely expressed throughout nature. As they participate in a number of different aspects of innate immunity in mammals, they have been termed Host Defense Peptides (HDPs). Due to their common structural features, including an amphipathic structure and cationic charge, they have been widely shown to interact with and disrupt microbial membranes. Thus, it is not surprising that human HDPs have activity against enveloped viruses as well as bacteria and fungi. However, these peptides also exhibit activity against a wide range of non-enveloped viruses as well, acting at a number of different steps in viral infection. This review focuses on the activity of human host defense peptides, including alpha- and beta-defensins and the sole human cathelicidin, LL-37, against both enveloped and non-enveloped viruses. The broad spectrum of antiviral activity of these peptides, both in vitro and in vivo suggest that they play an important role in the innate antiviral defense against viral infections. Furthermore, the literature suggests that they may be developed into antiviral therapeutic agents.

Human thrombin-derived host defense peptides inhibit neutrophil recruitment and tissue injury in severe acute pancreatitis

2014 ◽  
Vol 307 (9) ◽  
pp. G914-G921 ◽  
Author(s):  
Mohammed Merza ◽  
Milladur Rahman ◽  
Songen Zhang ◽  
Rundk Hwaiz ◽  
Sara Regner ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Host Defense ◽  
Tissue Injury ◽  
Intraperitoneal Administration ◽  
Protective Effects ◽  
Edema Formation ◽  
Host Defense Peptides ◽  
Defense Peptides

Severe acute pancreatitis (AP) is characterized by leukocyte infiltration and tissue injury. Herein, we wanted to examine the potential effects of thrombin-derived host defense peptides (TDPs) in severe AP. Pancreatitis was provoked by infusion of taurocholate into the pancreatic duct or by intraperitoneal administration of l-arginine in C57BL/6 mice. Animals were treated with the TDPs GKY20 and GKY25 or a control peptide WFF25 30 min before induction of AP. TDPs reduced blood amylase levels, neutrophil infiltration, hemorrhage, necrosis, and edema formation in the inflamed pancreas. Treatment with TDPs markedly attenuated the taurocholate-induced increase in plasma levels of CXCL2 and interleukin-6. Moreover, administration of TDPs decreased histone 3, histone 4, and myeloperoxidase levels in the pancreas in response to taurocholate challenge. Interestingly, administration of TDPs abolished neutrophil expression of Mac-1 in mice with pancreatitis. In addition, TDPs inhibited CXCL2-induced chemotaxis of isolated neutrophils in vitro. Fluorescent-labeled TDP was found to directly bind to isolated neutrophils. Finally, a beneficial effect of TDPs was confirmed in l-arginine-induced pancreatitis. Our novel results demonstrate that TDPs exert protective effects against pathological inflammation and tissue damage in AP. These findings suggest that TDPs might be useful in the management of patients with severe AP.

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