Autophagy increased pro-inflammatory cytokines against Listeria monocytogenes infection in macrophage

Abstract

Listeria monocytogenes, a Gram-positive intracellular pathogen, is a causative of listeriosis in both humans and animals. L. monocytogenes is known to evade host immunity, yet could be cleared by autophagy induction in macrophages. With this twist, we investigated the effect of autophagy inducing pro-inflammatory cytokines for protective immunity in bone marrow-derived macrophages (BMDMs) infected with L. monocytogenes. After the infection, autophagy induction by rapamycin reduced survival of intracellular L. monocytogenes while inhibition of autophagy enhances their survival. After 24 hours of L. monocytogenes infection, rapamycin-treated BMDMs produced interleukin (IL)-1β, IL-6, IL-12p40 higher than those of control group. As expected, autophagy inhibition reduced levels of cytokines compared with those of control. Treatment of heat killed L. monocytogenes, which acts as a TLR ligand without invasion, also showed a similar pattern with L. monocytogenes infection in BMDMs in terms of cytokine secretion, suggesting that modulation of pro-inflammatory cytokines by autophagy is TLR signaling dependent. The expression and nucleus translocation of interferon regulatory factor 5 (IRF5) that modulate IL-6 and IL-12 production, were increased in autophagy-induced BMDMs. In addition, degradation of IκBα, which is important for NF-κB activity, was increased by autophagy induction upon HKLM treated BMDMs. Taken together, rapamycin-induced autophagy enhances production of pro-inflammatory cytokines in BMDMs infected with L. monocytogenes.