Oleuropein activates autophagy to circumvent anti-plasmodial defense
Praveen Sharma,
Nikunj Tandel,
Rajinder Kumar,
Sushmita Negi,
Prakriti Sharma,
Sonia Devi,
Kanika Saxena,
Neil Roy Chaudhary,
Sheetal Saini,
Reetesh Kumar,
Bharat Singh Chandel,
Puran S. Sijwali,
Rajeev K. Tyagi
Affiliations
Praveen Sharma
Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India
Nikunj Tandel
Institute of Science, Nirma University, SG highway, Ahmedabad 382481, India
Rajinder Kumar
Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India
Sushmita Negi
Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India; Academy of Scientific and Innovation Research (AcSIR), Ghaziabad 201002, India
Prakriti Sharma
Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India
Sonia Devi
Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India; Academy of Scientific and Innovation Research (AcSIR), Ghaziabad 201002, India
Kanika Saxena
Academy of Scientific and Innovation Research (AcSIR), Ghaziabad 201002, India; CSIR-Centre for Cellular & Molecular Biology, Hyderabad, Telangana, India
Neil Roy Chaudhary
Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India
Sheetal Saini
Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India
Reetesh Kumar
Faculty of Agricultural Sciences, Institute of Applied Sciences & Humanities, GLA University, Mathura 281406, India
Bharat Singh Chandel
Department of Animal Biotechnology, College of Veterinary Science and AH, Sardarkrushinagar Dantiwada Agricultural University, Sardarkrushinagar, Gujarat 385 506, India
Puran S. Sijwali
Academy of Scientific and Innovation Research (AcSIR), Ghaziabad 201002, India; CSIR-Centre for Cellular & Molecular Biology, Hyderabad, Telangana, India
Rajeev K. Tyagi
Division of Cell Biology and Immunology, Biomedical Parasitology and Translational-immunology Lab, CSIR-Institute of Microbial Technology (IMTECH), Sec-39A, Chandigarh 160036, India; Academy of Scientific and Innovation Research (AcSIR), Ghaziabad 201002, India; Corresponding author
Summary: Antimalarial drug resistance and unavailability of effective vaccine warrant for newer drugs and drug targets. Hence, anti-inflammatory activity of phyto-compound (oleuropein; OLP) was determined in antigen (LPS)-stimulated human THP-1 macrophages (macrophage model of inflammation; MMI). Reduction in the inflammation was controlled by the PI3K-Akt1 signaling to establish the “immune-homeostasis.” Also, OLP treatment influenced the cell death/autophagy axis leading to the modulated inflammation for extended cell survival. The findings with MII prompted us to detect the antimalarial activity of OLP in the wild type (3D7), D10-expressing GFP-Atg18 parasite, and chloroquine-resistant (Dd2) parasite. OLP did not show the parasite inhibition in the routine in vitro culture of P. falciparum whereas OLP increased the antimalarial activity of artesunate. The molecular docking of autophagy-related proteins, investigations with MMI, and parasite inhibition assays indicated that the host activated the autophagy to survive OLP pressure. The challenge model of P. berghei infection showed to induce autophagy for circumventing anti-plasmodial defenses.
