Leukotriene B₄ is essential for lung host defence and alpha-defensin-1 production during Achromobacter xylosoxidans...

Leukotriene B₄ (LTB₄) 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 LTB₄ during Achromobacter xylosoxidans infection remain unexplored. Wild-type (129sv) and LTB₄ 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 LTB₄ in the lung on the 1^st day, while levels of PGE₂ 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 LTB₄ does not affect the phagocytosis of A. xylosoxidans by alveolar macrophages in vitro. However, treatment of infected animals with LTB₄ protected from mortality, by reducing the bacterial load and inflammation via BLT₁ signalling, the high affinity receptor for LTB₄. Of importance, we uncovered that LTB₄ 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 LTB₄ on the control of A. xylosoxidans infection.