Abstract
Despite a global effort to develop an effective vaccine, malaria is still a significant health problem. Much of the pathology of malaria is immune mediated. This suggests that host immune responses have to be finely regulated. The innate immune system initiates and sets the threshold of the acquired immune response and determines the outcome of the disease. Yet, our knowledge of the regulation of innate immune responses during malaria is limited. Theoretically, inadequate activation of the innate immune system could result in unrestrained parasite growth. Conversely, hyperactivation of the innate immune system, is likely to cause excessive production of proinflammatory cytokines and severe pathology. Toll-like receptors (TLRs) have emerged as essential receptors which detect signature molecules and shape the complex host response during malaria infection. This review will highlight the mechanisms by which Plasmodium components are recognized by innate immune receptors with particular emphasis on TLRs. A thorough understanding of the complex roles of TLRs in malaria may allow the delineation of pathological versus protective host responses and enhance the efficacy of anti-malarial treatments and vaccines.
Highlights
Malaria is one of the most devastating diseases of human history
In this review we focus on the interaction between host immune receptors ( Toll-like receptors (TLRs)) and malaria components, with the goal of understanding the host responses to Plasmodium and how the parasite modulates the immune system
We focus on recent studies that uncover the role of TLRs and other pattern-recognition receptors (PRRs) in the sensing of these molecules
Summary
Malaria is one of the most devastating diseases of human history. In many developing countries, malaria remains to be a significant health burden with around one million deaths per year, mostly in children under the age of five [1,2]. There has been a significant advance in the understanding of acquired immunity in malaria, the innate immune response to malaria has not been intensely scrutinized. An important aspect of the innate immune response is to trigger acquired immunity. Understanding this area of malaria biology should prove critical in the search for an efficacious malaria vaccine. Two major unresolved issues concerning the pathogenesis of malaria are: which components from the parasite activate the innate immune system to cause inflammation and, what are the host receptors that recognize these microbial products. In this review we focus on the interaction between host immune receptors ( TLRs) and malaria components, with the goal of understanding the host responses to Plasmodium and how the parasite modulates the immune system
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