Extracellular Histones Induce Chemokine Production in Whole Blood Ex Vivo and Leukocyte Recruitment In Vivo.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

The innate immune system relies to a great deal on the interaction of pattern recognition receptors with pathogen- or damage-associated molecular pattern molecules. Extracellular histones belong to the latter group and their release has been described to contribute to the induction of systemic inflammatory reactions. However, little is known about their functions in the early immune response to an invading pathogen. Here we show that extracellular histones specifically target monocytes in human blood and this evokes the mobilization of the chemotactic chemokines CXCL9 and CXCL10 from these cells. The chemokine induction involves the toll-like receptor 4/myeloid differentiation factor 2 complex on monocytes, and is under the control of interferon-γ. Consequently, subcutaneous challenge with extracellular histones results in elevated levels of CXCL10 in a murine air pouch model and an influx of leukocytes to the site of injection in a TLR4 dependent manner. When analyzing tissue biopsies from patients with necrotizing fasciitis caused by Streptococcus pyogenes, extracellular histone H4 and CXCL10 are immunostained in necrotic, but not healthy tissue. Collectively, these results show for the first time that extracellular histones have an important function as chemoattractants as their local release triggers the recruitment of immune cells to the site of infection.

Detaljer

Författare
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
Originalspråkengelska
Artikelnummere1005319
TidskriftPLoS Pathogens
Volym11
Utgåva nummer12
StatusPublished - 2015
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Westman, J., 2016, Avdelningen för Infektionsmedicin. 56 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

Visa alla (1)

Related projects

Heiko Herwald

2013/01/01 → …

Projekt: Forskning

Visa alla (1)