Severe malaria infection caused by Plasmodium falciparum is a global life-threatening disease and a leading cause of death worldwide. Intensive investigations have demonstrated that macrophages play crucial roles in control of inflammatory and immune responses and clearance of Plasmodium-falciparum-parasitized erythrocytes (PE). This paper focuses on how macrophage CD36 recognizes and internalizes PE and participates the inflammatory signaling in response to Plasmodium falciparum. In addition, recent advances in our current understanding of the biological actions of PPARγ on CD36 and malaria clearance from the hosts are highlighted. 1. Introduction Macrophages play a crucial role in the innate immunity [1] and are essential components of defense against the malaria infection. Macrophages can take up nonopsonic or opsonic Plasmodium-falciparum-parasitized erythrocytes (PE) by using CD36 and Fc receptors, respectively. Nonopsonic PE phagocytosis by macrophage CD36 plays a major role for PE clearance especially in the acute phase of primary malaria infection or nonimmune hosts [2, 3]. Therefore, upregulation of CD36 on macrophages could greatly trigger the capacity to clear parasites during acute malaria infection and thus is likely to be effective treatment for malaria infection. The intensive investigations demonstrate that peroxisome proliferator-activator receptor γ (PPARγ) plays an important role in the immune response via inhibiting the expression of inflammatory cytokines and control macrophage alternative activation [4–6] and has potential as a novel anti-inflammatory target for many inflammatory diseases [7] including parasitic infection [8–10]. CD36 can be induced by PPARγ ligands, and activation of PPARγ enhances the clearance of PE and inhibits the proinflammatory response [6, 11]. Here, we highlight recent advances in our current understanding of the biological actions of PPARγ on CD36 and malaria clearance from the hosts. 2. CD36 and Malaria Clearance Macrophages play a crucial role in innate immunity to malaria infection because they can phagocytose infected erythrocytes that limit the malaria density in the absence of cytophilic or opsonizing malaria-specific antibody [2]. Macrophage pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs) and scavenger receptors such as CD36, are important components in the regulation of immune and inflammatory responses [12]. PRRs are a class of innate immune response-expressed proteins that recognize a wide range of molecules known as pathogen-associated molecular patterns (PAMPs)
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