Responses and Infectivity of the Human Macrophage Cell-Line THP-1 to Chlorovirus ATCV-1 or its Major Capsid Protein Glycan are Dependent on the Macrophage Polarization Phenotype 2099

Abstract Description Macrophage cytokines, such as IL-6, are associated with inflammatory diseases such as Amyotrophic Lateral Sclerosis (ALS). Acanthocystis turfacea chlorella virus 1 (ATCV-1), which infect Chlorella heliozoae green alga, have been show to also infect murine macrophages and trigger production of IL-6. However, it is unclear if ATCV-1 or its Major Capsid Protein (MCP) Glycans induce responses from human macrophages with M0, M1, M2 phenotypes. Thus, human THP-1 Lucia macrophage cells that have an ISRE promoter-reporter were challenged with ATCV-1 or its MCP-glycans before and after polarization. Immature (IMM) THP-1 cells were differentiated to M0 with 150 nM TPA, to M1 with hIFN-g plus LPS or to M2 with hIL-4 and hIL-13. IMM, M0, M1, and M2 THP-1 Lucia cells were then challenged with ATCV-1 or its MCP. Herein, ATCV-1 infected M1 THP-1 significantly more than IMM, M0, or M2. M1 THP-1 had high ISRE-promoter activity, which was suppressed by MCP-Glycan. M0 THP-1 produced IL-6 only in response to ATCV-1 or MCP-glycan. In contrast, unchallenged M1 THP-1 produced high levels of IL-6, which stimulated further by ATCV-1 or its MCP-glycan. In contrast, unchallenged M2 THP-1 produced high levels of IL-10, which was significantly reduced by ATCV-1 or MCP-Glycan. Thus, exposure to ATCV-1 or its MCP glycans can stimulate human macrophage inflammatory cytokine IL-6 that is associated with several diseases, including ALS and can reduce production of anti-inflammatory cytokine IL-10. Funding Sources This work was supported by the Stuart Nichols ALS Research Foundation & THE NEBRASKA RESEARCH INITIATIVE Topic Categories Viral Immunology (VIR)