Autophagic induction modulates splenic plasmacytoid dendritic cell mediated immune response in cerebral malarial infection model |
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Authors: | Anirban Sengupta Tarun Keswani Samrat Sarkar Soubhik Ghosh Saikat Mukherjee Arindam Bhattacharyya |
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Institution: | 1. Immunology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700019, India;2. Basic and Clinical Immunology of Parasitic Diseases, Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 8204 - CIIL - Centre of Infection and Immunity Lille, F-59000 Lille, France, 1 Rue du Professeur Calmette, 59019, Lille, France |
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Abstract: | Splenic plasmacytoid dendritic cells (pDC) possess the capability to harbor live replicative Plasmodium parasite. Isolated splenic pDC from infected mice causes malaria when transferred to naïve mice. Incomplete autophagic degradation might cause poor antigen processing and poor immune response. Induction of autophagic flux by rapamycin treatment led to better prognosis by boosting pDC centered immune response against the pathogen. Splenic pDC from rapamycin-treated infected mice, caused less parasitemia in naïve mice. The downregulation of adhesion with unaltered phagocytic potential of the cells post autophagic induction restricted excessive parasite burden within them. Rapamycin-treated pDC played a better role in antigen presentation. They showed higher expression of co-stimulatory molecules CD80, CD86, DEC205, MHCI. Rapamycin-treated pDC induced CD28 expression on CD8+ T cells and suppressed FasL level. This cells also influenced differentiation of effector, memory T cell population. The increase in IL10: TNFα ratio, Treg: Th17 ratio and lowering of myeloid DC: plasmacytoid DC ratio was observed. It shifted the overaggressive inflammation mediated Th1 pathway that is reported to incur host damage, to a better well-balanced cytokine profile exhibiting Th2 pathway. Autophagic flux induction within pDC proved to be beneficial in combating malarial pathogenicity. |
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Keywords: | Corresponding author Cerebral malaria Autophagy pDC-antigen presentation mDC-pDC ratio Th1-Th2 immune response |
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