TLR2-Induced IL-10 Production Impairs Neutrophil Recruitment to Infected Tissues during Neonatal Bacterial Sepsis

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Elva B Andrade (Author) Other; Joana Alves (Author) Other; Pedro Madureira (Author) Other; Liliana Oliveira (Author) Other; Adilia Ribeiro (Author) Other; Anabela Cordeiro da Silva (Author) FFUP; Margarida Correia Neves (Author) Other; Patrick Trieu Cuot (Author) Other; Paula Ferreira (Author) ICBAS

Journal

Title: Journal of Immunology

Vol. 191

Pages: 4759-4768

ISSN: 0022-1767

Publisher: American Association of Immunologists

Indexing

ISI Web of Knowledge - 32 Citations

Scopus - 41 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-006-6AB

DOI: 10.4049/jimmunol.1301752

Abstract (EN): Sepsis is the third most common cause of neonatal death, with Group B Streptococcus (GBS) being the leading bacterial agent. The pathogenesis of neonatal septicemia is still unsolved. We described previously that host susceptibility to GBS infection is due to early IL-10 production. In this study, we investigated whether triggering TLR2 to produce IL-10 is a risk factor for neonatal bacterial sepsis. We observed that, in contrast to wild-type (WT) pups, neonatal TLR2-deficient mice were resistant to GBS-induced sepsis. Moreover, if IL-10 signaling were blocked in WT mice, they also were resistant to sepsis. This increased survival rate was due to an efficient recruitment of neutrophils to infected tissues that leads to bacterial clearance, thus preventing the development of sepsis. To confirm that IL-10 produced through TLR2 activation prevents neutrophil recruitment, WT pups were treated with the TLR2 agonist Pam3CSK4 prior to nebulization with the neutrophil chemotactic agent LTB4. Neutrophil recruitment into the neonatal lungs was inhibited in pups treated with Pam3CSK4. However, the migration was restored in Pam3CSK4-treated pups when IL-10 signaling was blocked (either by anti-IL-10R mAb treatment or by using IL-10-deficient mice). Our findings highlight that TLR2-induced IL-10 production is a key event in neonatal susceptibility to bacterial sepsis.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10