BTPA PROTEIN FROM BRUCELLA ABORTUS MODULATES THE INFLAMMATORY RESPONSE FROM LPS-INDUCED ACUTE LUNG INJURY

MUÑOZ GONZALEZ FLORENCIA; BALDI PABLO C; CERVO MARÍA VICTORIA; PAIVA ALONSO IVAN; CERVO MARÍA VICTORIA; PAIVA ALONSO IVAN; FOCARACCIO JULIETA; ZAVATTIERI LUCÍA; FERRERO MARIANA CRISTINA; FOCARACCIO JULIETA; ZAVATTIERI LUCÍA; FERRERO MARIANA CRISTINA; MUÑOZ GONZALEZ FLORENCIA; BALDI PABLO C

San Miguel de Tucumán

Congreso; LXVII Reunión Anual de al Sociedad Argentina de Inmunología; 2019

Sociedad Argentina de Inmunología

Acute lung injury (ALI) is defined as the result of uncontrolled inflammatory responses in the lungs, for which effective treatment is necessary. Brucella abortus expresses two TIR-containing proteins (BtpA and BtpB) that impair TLR4 signaling in dendritic cells. Previously we found that Btp proteins modulate the lung proinflammatory response to respiratory Brucella infection. In this study, we investigated the effect of recombinant BtpA on lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in a murine model of LPS-induced ALI. We assessed the effects of BtpA on LPS-induced production of TNF-α, IL-6, and IL-1β in the culture supernatants of murine marophages (RAW 264.7) and endothelial cells. Additionally, male mice were treated with BtpA (5 mg/kg) or dexamethasone as positive control (5 mg/kg) for 2 h prior to LPS (0.5 mg/kg) intratracheal challenge. Airway inflammation was assessed 24 h later. BtpA attenuated the lung histological changes induced by LPS and reduced TNF-α, IL-1β and IL-6 levels in bronchoalveolar lavage fluid (BAL, p< 0,0001). BtpA treatment also reduced the BAL counts of total cells, neutrophils and macrophages. In vitro, BtpA (10, 30 and 50 ug/ml) reduced the production of TNF-α and IL-6 in LPS-stimulated macrophages (p< 0,0001) and the IL-6 secretion in LPS-stimulated endothelial cells (p< 0,0001). Collectively, our results suggest that BtpA was an effective inhibitor of LPS-induced ALI, and may serve as a future treatment for ALI.