The zebrafish has become a powerful model organism to study host-pathogen interactions. Here, we developed a zebrafish model of
infection to dissect innate immune responses. We show that
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
. 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
invade and grow in the larval yolk region but not a T4SS mutant. Zebrafish larva represent an innovative
infection model closely mimicking important aspects of human infection.