Autophagy Protects Monocytes from Wolbachia Heat Shock Protein 60–Induced Apoptosis and Senescence

Monocyte dysfunction by filarial antigens has been a major mechanism underlying immune evasion following hyporesponsiveness during patent lymphatic filariasis. recent studies have initiated a paradigm shift to comprehend the immunological interactions of wolbachia and its antigens in inflammation,apoptosis,lymphocyte anergy,etc. here we showed that recombinant wolbachia heat shock protein 60 (rwmhsp60) interacts with tlr-4 and induces apoptosis in monocytes of endemic normal but not in chronic patients. higher levels of reactive oxygen species (ros) induced after tlr-4 stimulation resulted in loss of mitochondrial membrane potential and caspase cascade activation,which are the plausible reason for apoptosis. furthermore,release in ros owing to tlr-4 signaling resulted in the activation of nf-κb p65 nuclear translocation which leads to inflammation and apoptosis via tnf receptor pathway following the increase in il-6 and tnf-α level. here for the first time,we report that in addition to apoptosis,rwmhsp60 antigen in filarial pathogenesis also induces molecular senescence in monocytes. targeting tlr-4,therefore,presents a promising candidate for treating rwmhsp60-induced apoptosis and senescence. strikingly,induction of autophagy by rapamycin detains tlr-4 in late endosomes and subverts tlr-4-rwmhsp60 interaction,thus protecting tlr-4–mediated apoptosis and senescence. furthermore,rapamycin-induced monocytes were unresponsive to rwmhsp60,and activated lymphocytes following pha stimulation. this study demonstrates that autophagy mediates the degradation of tlr-4 signaling and protects monocytes from rwmhsp60 induced apoptosis and senescence.