| Antimicrobial Peptides Inhibit Polyinosinic-Polycytidylic Acid-Induced Immune Responses. | |
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MedLine Citation:
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PMID: 22048772 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Viral proteins and nucleic acids stimulate TLRs to elicit production of cytokines, chemokines, and IFNs. Because of their immunostimulatory activity, several TLR agonists are being developed as vaccine adjuvants and cancer immunotherapeutics. However, TLR signaling is modified by disease state, which could enhance or impair therapeutic efficacy. For example, in the skin of psoriasis patients, the human cationic antimicrobial peptide LL37 is highly expressed and binds to host DNA. Association with LL37 enhances DNA uptake into intracellular compartments, where it stimulates TLR9-dependent overproduction of IFNs. Polyinosinic-polycytidylic acid (poly(I:C)), an analog of viral dsRNA, is recognized by TLR3 and is currently in preclinical trials as an inducer of type I IFN. If LL37 similarly enhanced IFN production, use of poly(I:C) might be contraindicated in certain conditions where LL37 is elevated. In this study, we show that TLR3 signaling was not enhanced, but was dramatically inhibited, by LL37 or mouse cathelicidin-related antimicrobial peptide in macrophages, microglial cells, and dendritic cells. Inhibition correlated with formation of a strong complex between antimicrobial peptides and poly(I:C), which partially inhibited poly(I:C) binding to TLR3. Therefore, after injury or during existing acute or chronic inflammation, when LL37 levels are elevated, the therapeutic activity of poly(I:C) will be compromised. Our findings highlight the importance of using caution when therapeutically delivering nucleic acids as immunomodulators. |
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Authors:
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Maroof Hasan; Catarina Ruksznis; Yan Wang; Cynthia Anne Leifer |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-2 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: - ISSN: 1550-6606 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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