Listeria monocytogenes invasion in goat brain tissues: mechanisms of blood-brain barrier disruption and regulation of apoptosis and autophagy.

BACKGROUND

Listeria monocytogenes (LM), a zoonotic intracellular pathogen, causes fatal neurological infections in ruminants (e.g., goats) and humans. However, the mechanisms by which LM breaches the blood-brain barrier (BBB) and regulates neuronal programmed cell death (apoptosis/autophagy) remain unclear in caprine models-knowledge that is critical for livestock disease control. This study aimed to investigate the spatiotemporal invasion pathway of LM in goat central nervous system, its brain region-specific effects on apoptosis and autophagy, and the role of the Pink1/Parkin pathway in mitochondrial autophagy during LM infection.

METHODS

Goats were intravenously infected with LM to establish an intracranial infection model. Bacterial loads in brain tissues were quantified, and multiple techniques (immunofluorescence, TUNEL, immunohistochemistry, Western blot, qRT-PCR) were used to detect BBB integrity, apoptotic/autophagic markers, and related pathway proteins (E-cadherin/c-Met, Bcl-2/Bax, LC3B, Pink1/Parkin).

RESULTS

LM showed tropism for brainstem regions (midbrain, pons, medulla oblongata) with focal colonization in neurons and glial cells. BBB tight junction proteins (ZO-1, Claudin-1, Occludin) exhibited region-specific dysregulation; notably, an upregulation of Claudin-1 and Occludin was observed in the medulla, suggesting a localized compensatory response. LM infection was associated with the activation of the E-cadherin/c-Met pathway, potentially facilitating transendothelial and neuronal invasion. Apoptosis (Bcl-2/Bax imbalance) and autophagy (LC3B, Pink1/Parkin) were heterogeneously regulated across brain regions, with significant quantitative changes observed in the cerebrum, cerebellum, midbrain, and medulla.

CONCLUSION

LM invades goat brain tissues coinciding with BBB disruption, exhibits brainstem tropism, and modulates apoptosis and autophagy through region-specific pathways, providing novel insights into LM-induced neurological pathogenesis in ruminants.