OBJECTIVETo test the effect of the c-Met inhibitor cabozantinib in inhibiting infections by Listeria monocytogenes (LM) in mice.

METHODSC57BL/6 mice at 6 weeks of age were subjected to intraperitoneal injection of LM and randomized into 4 groups for treatment with intraperitoneal injection of PBS, intragastric administration of cabozantinib (20 µg/g), intraperitoneal injection of ampicillin (Amp, 20 µg/g), or cabozantinib plus Amp. The survival curves were drawn for each group, and the number of bacteria in the blood and brain tissues was determined; serum IL-10 level and NF-κB p65 level in the cerebrospinal fluid (CSF) were assayed, and Evans Blue (EB) content and pathological changes in brain were examined.

RESULTSCompared with PBS-treated mice, the mice treated with cabozantinib showed a significantly higher survival rate, lower bacterial counts in the blood and brain (P<0.05 or 0.001), lower IL-10 (P<0.05) and NF-κB p65 levels (P<0.01), lower brain EB content (P<0.001), and milder pathological changes in the brain. The blood and brain bacterial counts (P<0.001), IL-10 (P<0.01) and NF-κB p65 levels (P<0.001), and brain EB content (P<0.001) were all significantly lower in mice treated with the combination of drugs than in mice treated with cabozantinib alone.

CONCLUSIONCabozantinib can inhibit LM infection in mice and has important values in developing new anti-intracellular infection drug.