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Updated: Jul 21, 2025
An In vitro Co-infection Model to Study Plasmodium falciparum-HIV-1 Interactions in Human Primary Monocyte-derived Immune Cells
Published on: August 15, 2012
Administration of soluble gp130Fc disrupts M-1 macrophage polarization, dendritic cell activation, MDSC expansion and
Saikat Mukherjee1, Soubhik Ghosh1, Sriparna Bawali1
1Immunology Laboratory, Department of Zoology, University of Calcutta. 35, Ballygunge Circular Road, Kolkata-700019, West Bengal, India.
Abstract:
Regulatory effect of IL-6 on various immune cells plays a crucial role during experimental cerebral malaria pathogenesis. IL-6 neutralization can restore distorted ratios of myeloid dendritic cells and plasmacytoid dendritic cells as well as the balance between Th-17 and T-regulatory cells. IL-6 can also influence immune cells through classical and trans IL-6 signalling pathways. As trans IL-6 signalling is reportedly involved during malaria pathogenesis, we focused on studying the effects of trans IL-6 signalling blockade on various immune cell populations and how they regulate ECM progression. Results show that administration of sgp130Fc recombinant chimera protein lowers the parasitemia, increases the survivability of Plasmodium berghei ANKA infected mice, and restores the distorted ratios of M1/M2 macrophage, mDC/pDC, and Th-17/Treg. IL-6 trans signalling blockade has been found to affect both expansion of myeloid derived suppressor cells (MDSCs) and expression of inflammatory markers on them during Plasmodium berghei ANKA infection indicating that trans IL-6 signalling might regulate various immune cells and their function during ECM. In this work for the first time, we delineate the effect of sgp130Fc administration on influencing the immunological changes within the host secondary lymphoid organ during ECM induced by Plasmodium berghei ANKA infection.
Insights
Blocking IL-6 trans-signalling with sgp130Fc improves survival in experimental cerebral malaria by restoring immune cell balance and reducing parasite load.
Area of Science:
- Immunology
- Parasitology
- Cellular Biology
Background:
- Interleukin-6 (IL-6) significantly impacts immune cell regulation in experimental cerebral malaria (ECM).
- IL-6 influences immune cells via classical and trans-signalling pathways, with trans-signalling implicated in malaria pathogenesis.
- Restoring immune cell balance, such as myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), is crucial for managing ECM.
Purpose of the Study:
- To investigate the therapeutic potential of blocking IL-6 trans-signalling in ECM.
- To analyze the effects of sgp130Fc administration on immune cell populations and ECM progression.
- To elucidate the role of IL-6 trans-signalling in regulating immune responses during Plasmodium berghei ANKA infection.
Main Methods:
- Administration of sgp130Fc, a recombinant chimera protein blocking IL-6 trans-signalling.
- Monitoring parasitemia and survival rates in Plasmodium berghei ANKA infected mice.
- Assessing immune cell populations including macrophages (M1/M2), dendritic cells (mDC/pDC), T helper 17 (Th-17) cells, regulatory T (Treg) cells, and myeloid-derived suppressor cells (MDSCs).
- Evaluating inflammatory marker expression on immune cells within secondary lymphoid organs.
Main Results:
- sgp130Fc treatment significantly reduced parasitemia and increased survival in infected mice.
- Blockade of IL-6 trans-signalling restored skewed ratios of M1/M2 macrophages, mDC/pDC, and Th-17/Treg cells.
- sgp130Fc administration modulated the expansion and inflammatory marker expression of myeloid-derived suppressor cells (MDSCs).
Conclusions:
- IL-6 trans-signalling blockade is a promising therapeutic strategy for experimental cerebral malaria.
- sgp130Fc effectively modulates key immune cell populations and their functions during ECM.
- This study provides novel insights into the immunological mechanisms underlying IL-6 trans-signalling in malaria pathogenesis.
