Interaction of the core fragments of the LL-37 host defense peptide with actin

Even though skin and oral mucosae are continuously in contact with commensal and opportunistic microorganisms, they generally remain healthy and uninflamed. Host defense peptides (HDPs) make up the body’s first line of defense against many invading pathogens and are involved in the orchestration of innate immunity and the inflammatory response. In this study, we investigated the effect of two salivary HDPs, LL-37 and Hst1, on the inflammatory and antimicrobial response by skin and oral mucosa (gingiva) keratinocytes and fibroblasts. The potent antimicrobial chemokine CCL20 was investigated and compared with chemokines CCL2, CXCL1, CXCL8, and CCL27 and proinflammatory cytokines IL-1αand IL-6. Keratinocyte-fibroblast cocultures showed a synergistic increase in CCL20 secretion upon Hst1 and LL-37 exposure compared to monocultures. These cocultures also showed increased IL-6, CXCL1, CXCL8, and CCL2 secretion, which was IL-1αdependent. Secretion of the antimicrobial chemokine CCL20 was clearly IL-1αindependent. These results indicate that salivary peptides can stimulate skin as well as gingiva cells to secrete antimicrobial chemokines as part of the hosts’ defense to counteract infection.

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Innate Immunity and Host Defense Peptides in Veterinary Medicine

Journal of Veterinary Internal Medicine ◽

10.1111/j.1939-1676.2007.0038.x ◽

2008 ◽

Vol 22 (2) ◽

pp. 247-265 ◽

Cited By ~ 65

Author(s):

A. Linde ◽

C.R. Ross ◽

E.G. Davis ◽

L. Dib ◽

F. Blecha ◽

...

Keyword(s):

Innate Immunity ◽

Veterinary Medicine ◽

Host Defense ◽

Host Defense Peptides ◽

Defense Peptides

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Bacterial Response to Innate Immunity Host‐Defense Peptides: Parameters Involved in Pathogen Resistance and Specificity

The FASEB Journal ◽

10.1096/fasebj.21.6.lb15-d ◽

2007 ◽

Vol 21 (6) ◽

Author(s):

Adi Peleg ◽

Yosef Rosenfeld ◽

Yechiel Shai

Keyword(s):

Innate Immunity ◽

Host Defense ◽

Pathogen Resistance ◽

Host Defense Peptides ◽

Bacterial Response ◽

Defense Peptides

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

Infection and Immunity ◽

10.1128/iai.74.4.2338-2352.2006 ◽

2006 ◽

Vol 74 (4) ◽

pp. 2338-2352 ◽

Cited By ~ 49

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms10093951 ◽

2009 ◽

Vol 10 (9) ◽

pp. 3951-3970 ◽

Cited By ~ 55

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

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Host Defense Peptide Resistance Contributes to Colonization and Maximal Intestinal Pathology by Crohn's Disease-Associated Adherent-Invasive Escherichia coli

Infection and Immunity ◽

10.1128/iai.01888-14 ◽

2014 ◽

Vol 82 (8) ◽

pp. 3383-3393 ◽

Cited By ~ 25

Author(s):

Joseph B. McPhee ◽

Cherrie L. Small ◽

Sarah A. Reid-Yu ◽

John R. Brannon ◽

Hervé Le Moual ◽

...

Keyword(s):

Escherichia Coli ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Host Defense ◽

Bacterial Killing ◽

Host Defense Peptides ◽

Content Type ◽

Host Defense Peptide ◽

Defense Peptides ◽

High Level

ABSTRACTHost defense peptides secreted by colonocytes and Paneth cells play a key role in innate host defenses in the gut. In Crohn's disease, the burden of tissue-associatedEscherichia colicommonly increases at epithelial surfaces where host defense peptides concentrate, suggesting that this bacterial population might actively resist this mechanism of bacterial killing. Adherent-invasiveE. coli(AIEC) is associated with Crohn's disease; however, the colonization determinants of AIEC in the inflamed gut are undefined. Here, we establish that host defense peptide resistance contributes to host colonization by Crohn's-associated AIEC. We identified a plasmid-encoded genomic island (called PI-6) in AIEC strain NRG857c that confers high-level resistance to α-helical cationic peptides and α- and β-defensins. Deletion of PI-6 sensitized strain NRG857c to these host defense molecules, reduced its competitive fitness in a mouse model of infection, and attenuated its ability to induce cecal pathology. This phenotype is due to two genes in PI-6,arlA, which encodes a Mig-14 family protein implicated in defensin resistance, andarlC, an OmpT family outer membrane protease. Implicit in these findings are new bacterial targets whose inhibition might limit AIEC burden and disease in the gut.

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Host Defense Peptide-Mimicking Polymers and Polymeric-Brush-Tethered Host Defense Peptides: Recent Developments, Limitations, and Potential Success

Pharmaceutics ◽

10.3390/pharmaceutics13111820 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1820

Author(s):

Hashem Etayash ◽

Robert E. W. Hancock

Keyword(s):

Host Defense ◽

Antibacterial Properties ◽

Research Area ◽

Host Defense Peptides ◽

Antimicrobial Polymers ◽

Bacterial Drug Resistance ◽

Recent Developments ◽

Host Defense Peptide ◽

Potential Success ◽

Defense Peptides

Amphiphilic antimicrobial polymers have attracted considerable interest as structural mimics of host defense peptides (HDPs) that provide a broad spectrum of activity and do not induce bacterial-drug resistance. Likewise, surface engineered polymeric-brush-tethered HDP is considered a promising coating strategy that prevents infections and endows implantable materials and medical devices with antifouling and antibacterial properties. While each strategy takes a different approach, both aim to circumvent limitations of HDPs, enhance physicochemical properties, therapeutic performance, and enable solutions to unmet therapeutic needs. In this review, we discuss the recent advances in each approach, spotlight the fundamental principles, describe current developments with examples, discuss benefits and limitations, and highlight potential success. The review intends to summarize our knowledge in this research area and stimulate further work on antimicrobial polymers and functionalized polymeric biomaterials as strategies to fight infectious diseases.

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