The
zebrafish,
Danio rerio, has become a popular vertebrate model for the study of
infections, mainly because of its excellent optical accessibility at the
embryonic and
larval stages, when the
innate immune system is already effective. We have thus tested the susceptibility of
zebrafish larvae to the human
pathogen Listeria monocytogenes, a
gram-positive, facultative,
intracellular bacterium that is known to survive and multiply in professional
phagocytes and that causes fatal
meningitis and
abortions.
Intravenous injection of early
zebrafish larvae resulted in a progressive and ultimately fatal
infection.
Blood-borne L. monocytogenes bacteria were quickly trapped and engulfed by
macrophages, an event that, for the first time, could be captured in vivo and in real time.
Granulocytes also participated in the
innate immune response. As in mammals,
bacteria could escape the
macrophage phagosome in a listeriolysin-dependent manner and accessed the
cytosol; this event was critical for
bacterial virulence, as listeriolysin-deficient
bacteria were completely
avirulent.
Actin comet
tails and protrusions were observed, suggesting cell-to-cell spread; these phenomena also played a role in
virulence in
zebrafish larvae, as actA-deficient
bacteria were
attenuated. These results demonstrate the relevance of the
genetically tractable and optically accessible
zebrafish model for the study of
L. monocytogenes pathogenesis and particularly for the
dissection of its interactions with
phagocytes in vivo, a key factor of
L. monocytogenes virulence.
