However, the results have been inconsistent (Table?2)
However, the results have been inconsistent (Table?2). and -thalassemia heterozygotes (_/) and homozygotes (_/_) are protected against severe malaria.8 However, these well-characterized polymorphisms only partially explain the genetic variation in responses to malaria. 12 It is important to identify additional human genetic variants that are associated with susceptibility or protection. Genetic variants of human killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigens (HLAs) are strongly associated with the risk of infectious diseases,13 autoimmune disorders,13C15 success in cell transplantation for the treatment of hematopoietic malignancies,16 certain cancers,17 and pregnancy outcomes.18 The and genes segregate independently on chromosomes 19 and 6, respectively; both gene families are highly diverse, with extensive allelic polymorphism.19 and genes are reported to be more polymorphic in African populations than in other populations.19 Evolutionary pressure from malaria pathogens may have partly driven the high and genetic diversity in Africa.20,21 The data regarding associations between AZD3463 and variants and malaria risk have been inconsistent, but since interactions between the genetically diverse KIR and HLA molecules modulate the functionality of the natural killer (NK) cell response to malaria infections, these genes remain good candidates for elucidating the role of immune cells in malaria. Despite recent reports indicating improvement in the control of malaria in some populations and the potential for the elimination of malaria from many regions Rabbit Monoclonal to KSHV ORF8 of the world, malaria still causes extensive morbidity and mortality, particularly in sub-Saharan Africa.22 In response to the persistent malaria burden, there have been increased efforts exerted in vector control using insecticides and malaria treatment and chemoprevention using antimalarial drugs.23 However, these approaches have faced challenges arising from both insecticide and drug resistance. 24 Antimalarial drug discovery is challenging and costly, 24 and parasite resistance develops easily.25 Given the limitations of insecticides and antimalarial drugs, a highly effective malaria vaccine would significantly contribute to malaria control.26 The major challenges to the development of vaccines against malaria include a failure to induce strong innate immune responses and a lack of potentiation and maintenance of adaptive immune responses.27 There have been efforts to develop malaria vaccines since the 1940s.28 Despite several promising candidates, an effective vaccine that provides long-lived protection against malaria has not been developed.29 One vaccine candidate, RTS,S/AS01, has recently been approved for pilot implementation trials in sub-Saharan Africa.30 However, RTS,S/AS01 offers only modest short-term protection,31,32 and the efficacy of this vaccine varies with the malaria transmission intensity.27 Other approaches are under study, but none have yet yielded a highly efficacious vaccine.32 A better understanding of the role of human genetic variation in heterogeneous immune responses to malaria infection may facilitate vaccine development. In this review, AZD3463 we provide a concise overview of the evidence for associations between and genetic variants and susceptibility to or protection against malaria. Killer-cell immunoglobulin-like receptors KIRs are a family of highly polymorphic type 1 transmembrane glycoproteins expressed on the surface of NK cells and some T cells33 that bind HLA class I molecules34 and regulate NK cell functions.35 KIRs are encoded by a AZD3463 set of highly polymorphic genes located within the leukocyte receptor complex on human chromosome 19q13.4.36 The are the second most genetically diverse family in the mammalian genome after genes, and they differ between individuals at three main levels: copy number variation, allelic diversity and variation in the binding specificity of individual to class I ligands.37 Sixteen genes have been described to date, including genes that encode both inhibitory (and is unique because it.