Autophagy inhibits nuclear factor kappa B and mitogen-activated protein kinase (MAPK) inflammatory signaling pathways and modulates cytokine release in murine microglia following Streptococcus suis serotype 2 infection

Abstract

Autophagy within macrophages serves as a vital mechanism for modulating inflammatory responses to central nervous system infections caused by Streptococcus suis in both humans and swine. However, the mechanism by which autophagy regulates inflammation during S. suis infection is unclear. This study investigated the mechanism by which autophagy serves as a defense against S. suis infection in mouse microglial cells (BV2). Initially, we examined how S. suis infection triggers the adenosine monophosphate-activated protein kinase (AMPK)/ mammalian target of rapamycin (mTOR) autophagic cascade and the nuclear factor kappa B (NF-κB) and, mitogen-activated protein kinase (MAPK) inflammatory signaling pathways using western blot within BV2 cells. We then demonstrated that treatment with autophagy inhibitors, inducers, and siRNA of autophagy genes changed the levels of C-C motif ligand 2 (CCL2), CCL3, CCL5, and tumor necrosis factor α (TNF-α), and p-p65, p-p38, p- c-Jun N-terminal kinase (JNK) and p-Extracellular signal-regulated kinase (ERK) activity within BV2 cells. We found that S. suis infection induced AMPK/mTOR autophagy pathway, NF-κB and MAPK pathway in BV2 cells. Further, Autophagy inhibits S. suis infection-induced NF-κB and MAPK signaling and subsequent inflammatory factors CCL2, CCL3, CCL5, and TNF-α. Collectively, these findings suggest that AMPK/mTOR-regulated autophagy has an inhibitory effect on pro-inflammatory cytokines and chemokines by regulating the NF-κB and MAPK pathways during S. suis infection.