Neutrophils play important roles in innate immunity and are mainly dependent on various enzyme-containing granules to kill engulfed microorganisms. Zebrafish
nephrosin
(
npsn
) is specifically expressed in neutrophils; however, its function is largely unknown. Here, we generated an
npsn
mutant (
npsn
smu5
) via CRISPR/Cas9 to investigate the
in vivo
function of Npsn. The overall development and number of neutrophils remained unchanged in
npsn
-deficient mutants, whereas neutrophil antibacterial function was defective. Upon infection with
Escherichia coli
, the
npsn
smu5
mutants exhibited a lower survival rate and more severe bacterial burden, as well as augmented inflammatory response to challenge with infection when compared with wild-type embryos, whereas
npsn
-overexpressing zebrafish exhibited enhanced host defence against
E. coli
infection. These findings demonstrated that zebrafish Npsn promotes host defence against bacterial infection. Furthermore, our findings suggested that
npsn
-deficient and -overexpressing zebrafish might serve as effective models of
in vivo
innate immunity.