Antimicrobial peptides versus invasive infections.

Abstract:

:It has been estimated that there are more microorganisms within and upon the human body than there are human cells. By necessity, every accessible niche must be defended by innate mechanisms to prevent invasive infection, and ideally that precludes the need for robust inflammatory responses. Yet the potential for pathogens to transcend the integument actively or passively and access the bloodstream emphasizes the need for rapid and potent antimicrobial defense mechanisms within the vascular compartment. Antimicrobial peptides from leukocytes have long been contemplated as being integral to defense against these infections. Recently, platelets are increasingly recognized for their likely multiple roles in antimicrobial host defense. Platelets and leukocytes share many structural and functional archetypes. Once activated, both cell types respond in specific ways that emphasize key roles for their antimicrobial peptides in host defense efficacy: (a) targeted accumulation at sites of tissue injury or infection; (b) direct interaction with pathogens; and (c) deployment of intracellular (leukocyte phagosomes) or extracellular (platelet secretion) antimicrobial peptides. Antimicrobial peptides from these cells exert rapid, potent, and direct antimicrobial effects against organisms that commonly access the bloodstream. Experimental models in vitro and in vivo show that antimicrobial peptides from these cells significantly contribute to prevent or limit infection. Moreover, certain platelet antimicrobial proteins are multifunctional kinocidins (microbicidal chemokines) that recruit leukocytes to sites of infection, and potentiate the antimicrobial mechanisms of these cells. In turn, pathogens pre-decorated by kinocidins may be more efficiently phagocytosed and killed by leukocytes and their antimicrobial peptide arsenal. Hence, multiple and relevant interactions between platelets and leukocytes have immunologic functions yet to be fully understood. A clearer definition of these interactions, and the antimicrobial peptide effectors contributing to these functions, will significantly advance our understanding of antimicrobial host defense against invasive infection. In addition, this knowledge may accelerate development of novel anti-infective agents and strategies against pathogens that have become refractory to conventional antimicrobials.

authors

Yeaman MR,Bayer AS

doi

10.1007/3-540-29916-5_5

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

111-52

eissn

0070-217X

issn

2196-9965

journal_volume

306

pub_type

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