Plasmodium falciparum RIFINS: Role in malariapathogenesis

Malaria kills an estimated 600,000 people each year, especially children under five years who reside in sub-SaharanAfrica. Malaria fatalities are associated with severe forms such as cerebral malaria, acute respiratory failure, severeanaemia, renal failure, hypoglycaemia, and pulmonary oedema. Although the underlying pathogenic mechanismsin immune responses and parasite immune evasion, cytoadherence of parasitized red blood cells, and rosetting areenumerated, the mechanisms are not fully understood. P. falciparum parasite-derived surface protein, repetitiveinterspersed family (RIFIN) genes are involved in rosetting, blocking microcirculation, and playing a role in malariapathogenesis; it is unclear which RIFIN family genes are involved in the various pathogenic mechanisms in malaria.RIFINs are the extensive malaria family genes expressed throughout the malaria parasite stages, indicating theirdiverse roles. Malaria pathogenesis occurs in erythrocyte-stage infection, and the expression of RIFINs at this phasecould play a diverse role in the various pathogenic mechanisms. They are involved in major phenomena such ascytoadherence, merozoite evasion, and immune evasion. RIFINs aid in the immune evasion of P. falciparum throughvarious molecular interactions by binding to the inhibitory receptors LAIR1, LILRB1, and LILRB2. RIFINs in severeforms of malaria (such as cerebral malaria and severe anaemia) require a considerable understanding to target andcontrol malaria severity and mortality. RIFINs are implicated in severe malaria and are discussed together with othervariant surface antigens such as STEVORS or PfEMP1 in the specific pathophysiology of malaria. This review detailsthe role of RIFINs in the various malaria pathophysiological mechanisms underlying severe malaria and mortality
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