Effector mechanisms induced by IFN-γ during malaria.

<p>Various immune cell subsets produce IFN-γ in response to <i>Plasmodium</i> infection. NK, γδ, and NKT cells are largely responsible for early production of IFN-γ in response to liver and blood stages of the parasite and play a role in early control of parasite growth. IFN-γ-producing CD8⁺ T cells have also been shown to limit intrahepatic parasite growth through an IFN-γ-inducible, nitric oxide-dependent mechanism (<b>1</b>). Once an adaptive immune response is initiated, IFN-γ produced by CD4⁺ T cells optimally activates CD8⁺ T cells, B cells, and macrophages. IFN-γ influences isotype switching in B cells leading to production of cytophilic antibodies capable of binding free parasites and blocking red blood cell invasion (<b>2</b>), mediating parasite clearance through opsonization (<b>3</b>), and binding the surface of infected red blood cells promoting antibody-dependent phagocytosis (<b>4</b>). Production of IFN-γ from CD4⁺ T cells also optimally activates macrophages to phagocytose infected red blood cells and free parasites (<b>5</b>). All of these mechanisms are important for optimal control of parasite growth during <i>Plasmodium</i> infection.