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Nucleic acid scavenging polymers inhibit extracellular DNA-mediated innate immune activation without inhibiting anti-viral responses.

Publication ,  Journal Article
Holl, EK; Shumansky, KL; Pitoc, G; Ramsburg, E; Sullenger, BA
Published in: PLoS One
2013

Toll-like receptor (TLR) family members, 3, 7 and 9 are key components in initiation and progression of autoimmune disorders such as systemic lupus erythematosus (SLE). These TLRs are often referred to as nucleic acid-sensing TLRs based on their ability to recognize DNAs or RNAs produced by pathogens or damaged cells. During autoimmune disease progression these receptors recognize self nucleic acids as well as self nucleic acid-containing complexes and contribute to inflammatory cytokine production and subsequent enhancement of serum autoantibody levels. We have recently discovered that nucleic-acid scavenging polymers (NASPs) can neutralize the proinflammatory effects of nucleic acids. Here, we begin to explore what effects such NASPs have on normal immune function. We show that such NASPs can inhibit TLR activation without affecting nucleic acid-independent T cell activation. Moreover, we observe that stimulation of immune cells by encapsulated nucleic acids, such as those found in viral particles, is unaffected by NASPs. Thus NASPs only limit the activation of the immune system by accessible extra-cellular nucleic acid and do not engender non-specific immune suppression. These important findings suggest that NASPs represent a new approach toward anti-inflammatory drug development as these agents can potentially be utilized to block overt autoimmune disorders and inflammation while allowing normal immune responses to occur.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

7

Start / End Page

e69413

Location

United States

Related Subject Headings

  • Virus Diseases
  • Receptors, Immunologic
  • Polymers
  • Phagocytosis
  • Ovalbumin
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Activation
  • Immunity, Innate
  • Histocompatibility Antigens Class II
 

Citation

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Holl, E. K., Shumansky, K. L., Pitoc, G., Ramsburg, E., & Sullenger, B. A. (2013). Nucleic acid scavenging polymers inhibit extracellular DNA-mediated innate immune activation without inhibiting anti-viral responses. PLoS One, 8(7), e69413. https://doi.org/10.1371/journal.pone.0069413
Holl, Eda K., Kara L. Shumansky, George Pitoc, Elizabeth Ramsburg, and Bruce A. Sullenger. “Nucleic acid scavenging polymers inhibit extracellular DNA-mediated innate immune activation without inhibiting anti-viral responses.PLoS One 8, no. 7 (2013): e69413. https://doi.org/10.1371/journal.pone.0069413.
Holl, Eda K., et al. “Nucleic acid scavenging polymers inhibit extracellular DNA-mediated innate immune activation without inhibiting anti-viral responses.PLoS One, vol. 8, no. 7, 2013, p. e69413. Pubmed, doi:10.1371/journal.pone.0069413.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

7

Start / End Page

e69413

Location

United States

Related Subject Headings

  • Virus Diseases
  • Receptors, Immunologic
  • Polymers
  • Phagocytosis
  • Ovalbumin
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Activation
  • Immunity, Innate
  • Histocompatibility Antigens Class II