Leukotriene B(4) is essential for lung host defence and alpha-defensin-1 production during Achromobacter xylosoxidans infection

Leukotriene B(4) (LTB(4)) is essential for host immune defence. It increases neutrophil recruitment, phagocytosis and pathogen clearance, and decreases oedema and inflammasome activation. The host response and the role of LTB(4) during Achromobacter xylosoxidans infection remain unexplored. Wild-type (129sv) and LTB(4) deficient (Alox5 (−/−)) mice were intratracheally infected with A. xylosoxidans. Wild-type 129sv infected mice survived beyond the 8(th) day post-infection, exhibited increased levels of LTB(4) in the lung on the 1(st) day, while levels of PGE(2) increased on the 7(th) day post-infection. Infected Alox5 (−/−) mice showed impaired bacterial clearance, increased lung inflammation, and succumbed to the infection by the 7(th) day. We found that exogenous LTB(4) does not affect the phagocytosis of A. xylosoxidans by alveolar macrophages in vitro. However, treatment of infected animals with LTB(4) protected from mortality, by reducing the bacterial load and inflammation via BLT(1) signalling, the high affinity receptor for LTB(4). Of importance, we uncovered that LTB(4) induces gene and protein expression of α-defensin-1 during the infection. This molecule is essential for bacterial clearance and exhibits potent antimicrobial activity by disrupting A. xylosoxidans cell wall. Taken together, our data demonstrate a major role for LTB(4) on the control of A. xylosoxidans infection.