Serum amyloid A and apolipoprotein E alter the host innate immune response elicited by malarial hemozoin (68.14)

Abstract

Abstract Malaria is one of the most important infectious diseases worldwide and still remains to be the major cause of death in tropical countries. The intraerythrocytic stage of the malaria parasite results in the production and release of hemozoin (HZ). Recently we have identified that HZ specifically interacts with serum proteins such as serum amyloid A (SAA) and apolipoprotein E (ApoE). In our current work, we were interested to determine the impact of these proteins on the macrophage’s innate immune response triggered by HZ. Since HZ induces IL-1β production via the NLRP3 inflammasome, we looked at the production of IL-1β using PMA-differentiated THP-1 cells. IL-1β, along with TNF-α, is considered to be the major contributor for malaria pathology. Our results show that SAA bound to HZ induces the production of IL-1β in a dose dependent manner. Furthermore, HZ-SAA and hemozoin-ApoE complexes phosphorylate the MAPKs specifically ERK1/2 and JNK. This is in agreement with the observation that SAA activates downstream signaling pathways via LYN resulting in the activation of ERK1/2 and JNK. Apart from IL-1β production, HZ bound serum proteins also modulate ROS production and phagocytosis in THP-1 cells. Overall, our results show that serum inflammatory proteins adhering on HZ modify its capacity to stimulate phagocytosis, IL-1β and ROS productions by THP-1 cells upon stimulation, suggesting that such cooperation could greatly influence the development of malaria-related pathologies.