PT  - JOURNAL ARTICLE
AU  - Davide Grandolfo
AU  - Andrew Thorley
AU  - Teresa Tetley
TI  - Late-breaking abstract: Activation of the macrophage inflammasome by TLR3 ligation potentiates release of IL-8 and IP-10 from alveolar type II epithelial cells via a paracrine cytokine network
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - 1443
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/1443.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/1443.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Recognition of microbial ligands by Toll-like receptors is central to the innate immune response of the peripheral lung to infection.This study investigated the effect of TLR3 ligation on cytokine release by primary human alveolar type II epithelial (ATII) cells and macrophages (AMs) alone and in co-culture. We hypothesised that TLR3 ligation elicits a distinct cytokine profile in both cell types which is enhanced by co-culture.Monocultures and co-cultures of ATII cells and AMs were were exposed to the TLR3 ligand PolyI:C for 24h. Both cells released IL-8 and IP-10 in response to PolyI:C; co-culture significantly potentiated their release 4- and 5.7-fold respectively (P<0.0001). The potentiation was not ATII:AM cell contact dependent; addition of Poly I:C treated AM conditioned medium to ATII monocultures maintained the response whereas conditioned medium from ATII cells did not induce potentiated release from AMs. To elucidate which macrophage-derived cytokines were responsible for the potentiated response, neutralising antibodies were added to conditioned medium from AMs prior to incubation with ATII monocultures. Results demonstrated that neutralization of inflammasome-related cytokines, IL-1β and IL-18, significantly inhibited release of IL-8 and IP-10 (Table1).View this table:Inhibition of cytokine release from ATII cellsIn conclusion, our study demonstrates that TLR3 ligands activate the AM inflammasome, inducing release of IL-1β and IL-18 which potentiates the innate immune response of the alveolar epithelium.