An <em>In Vitro</em> Model for Measuring Immune Responses to Malaria in the Context of HIV Co-infection

Abstract

Malaria and HIV co-infection is a growing health priority. However, most research on malaria or HIV currently focuses on each infection individually. Although understanding the disease dynamics for each of these pathogens independently is vital, it is also important that the interactions between these pathogens are investigated and understood.We have developed a versatile in vitro model of HIV-malaria co-infection to study host immune responses to malaria in the context of HIV infection. Our model allows the study of secreted factors in cellular supernatants, cell surface and intracellular protein markers, as well as RNA expression levels. The experimental design and methods used limit variability and promote data reliability and reproducibility.All pathogens used in this model are natural human pathogens (Plasmodium falciparum and HIV-1), and all infected cells are naturally infected and used fresh. We use human erythrocytes parasitized with P. falciparum and maintained in continuous in vitro culture. We obtain freshly isolated peripheral blood mononuclear cells from chronically HIV-infected volunteers. Every condition used has an appropriate control (P. falciparum parasitized vs. normal erythrocytes), and every HIV-infected donor has an HIV uninfected control, from which cells are harvested on the same day. This model provides a realistic environment to study the interactions between malaria parasites and human immune cells in the context of HIV infection. Video LinkThe video component of this article can be found at

Experimental systems for studying Plasmodium/HIV coinfection

“…A variation in this experimental setup employed PBMCs isolated from HIV‐infected individuals for coculture with Plasmodium‐infected red blood cells and also observed changes in the proinflammatory response to infection. In contrast to the study using experimental ex vivo infection with HIV, proinflammatory responses were reduced upon coinfection in this case . These different outcomes may reflect that the rates of productive HIV infection are much lower in patient samples as compared to experimental ex vivo infections and that the boost in proinflammatory cytokine release can only be observed if a minimal threshold of HIV replication is achieved.…”