Expression and Function of Host Defense Peptides at Inflammation Sites

There is a growing interest in the complex role of host defense peptides (HDPs) in the pathophysiology of several immune-mediated inflammatory diseases. The physicochemical properties and selective interaction of HDPs with various receptors define their immunomodulatory effects. However, it is quite challenging to understand their function because some HDPs play opposing pro-inflammatory and anti-inflammatory roles, depending on their expression level within the site of inflammation. While it is known that HDPs maintain constitutive host protection against invading microorganisms, the inducible nature of HDPs in various cells and tissues is an important aspect of the molecular events of inflammation. This review outlines the biological functions and emerging roles of HDPs in different inflammatory conditions. We further discuss the current data on the clinical relevance of impaired HDPs expression in inflammation and selected diseases.

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Peptide Antimicrobial Agents

Clinical Microbiology Reviews ◽

10.1128/cmr.00056-05 ◽

2006 ◽

Vol 19 (3) ◽

pp. 491-511 ◽

Cited By ~ 1429

Author(s):

Håvard Jenssen ◽

Pamela Hamill ◽

Robert E. W. Hancock

Keyword(s):

Host Defense ◽

Antimicrobial Agents ◽

Antibacterial Activities ◽

Antimicrobial Activities ◽

Host Defense Peptides ◽

Important Host ◽

Defense Peptides ◽

And Function ◽

The Relationship ◽

Defense Molecules

SUMMARY Antimicrobial host defense peptides are produced by all complex organisms as well as some microbes and have diverse and complex antimicrobial activities. Collectively these peptides demonstrate a broad range of antiviral and antibacterial activities and modes of action, and it is important to distinguish between direct microbicidal and indirect activities against such pathogens. The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides. Peptides with antifungal and antiparasitic activities are discussed in less detail, although the broad-spectrum activities of such peptides indicate that they are important host defense molecules. Knowledge regarding the relationship between peptide structure and function as well as their mechanism of action is being applied in the design of antimicrobial peptide variants as potential novel therapeutic agents.

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Geographically Distinct Expression Profile of Host Defense Peptides in the Skin of the Chinese Odorous Frog, Odorrana margaretae

Asian Herpetological Research ◽

10.3724/sp.j.1245.2013.00288 ◽

2014 ◽

Vol 4 (4) ◽

pp. 288-297

Author(s):

LING Guiying ◽

LI Li ◽

GAO Jiuxiang ◽

YU Haining ◽

WANG Yipeng ◽

...

Keyword(s):

Host Defense ◽

Expression Profile ◽

Host Defense Peptides ◽

Defense Peptides

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Human Host Defense Peptides - Role in Maintaining Human Homeostasis and Pathological Processes

Current Medicinal Chemistry ◽

10.2174/0929867323666161213100443 ◽

2017 ◽

Vol 24 (7) ◽

pp. 654-672 ◽

Cited By ~ 2

Author(s):

Malgorzata Anna Dawgul ◽

Katarzyna E. Greber ◽

Wieslaw Sawicki ◽

Wojciech Kamysz

Keyword(s):

Host Defense ◽

Host Defense Peptides ◽

Human Host ◽

Defense Peptides

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

Antibiotics ◽

10.3390/antibiotics10040404 ◽

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.

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