Zebrafish larvae as a powerful model to dissect protective innate immunity in response to Legionella pneumophila infection

The zebrafish has become a powerful model organism to study host-pathogen interactions. Here, we developed a zebrafish model of Legionella pneumophila infection to dissect innate immune responses. We show that L. pneumophila cause zebrafish larvae death in a dose dependent manner, and that macrophages are the first line of defence, with neutrophils cooperating to clear the infection. When either macrophages or neutrophils are depleted, the larvae become lethally sensitive to L. pneumophila . As observed in human infections, the adaptor signalling molecule Myd88 is not required to control disease in the larvae. Furthermore, proinflammatory cytokines IL-1β and TNFα were upregulated during infection, recapitulating key immune responses seen in human infection. We also uncovered a previously undescribed phenotype in zebrafish larvae, whereby bloodborne, wild type L. pneumophila invade and grow in the larval yolk region but not a T4SS mutant. Zebrafish larva represent an innovative L. pneumophila infection model closely mimicking important aspects of human infection.