Preliminary Report on the Putative Association of Il10 -3575 T/a Genetic Polymorphism With Malaria Symptoms

Domingues, Wilson; Kanunfre, Kelly Aparecida; Rodrigues, Jonatas Cristian; Teixeira, Leandro Emidio; Yamamoto, Lídia; Okay, Thelma Suely

doi:10.1590/s1678-9946201658030

Cited by 9 publications

(6 citation statements)

References 40 publications

(47 reference statements)

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“…IL-10 is a key immuno-regulator of immunity to infections [85] and has been associated with various malaria-related phenotypes, such as uncomplicated malaria, severe malaria, severe malaria anaemia and high parasite density [86][87][88][89][90][91]. In addition, a number of studies have reported associations between IL-10 SNPs and susceptibility to malaria with either protective effects in some SNPs and increased susceptibility in others [72,[92][93][94][95]. Therefore, this tendency of an increased risk of malaria among carriers of rs1800890 SNP in IL-10 gene, could results from changes that do not allow adequate modulation of inflammatory responses since IL-10 is an anti-inflammatory cytokine.…”

Section: Discussionmentioning

confidence: 99%

Genetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina Faso

Natama

Rovira-Vallbona

Krit

et al. 2021

Malar J

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Background Genetic polymorphisms in the human immune system modulate susceptibility to malaria. However, there is a paucity of data on the contribution of immunogenetic variants to malaria susceptibility in infants, who present differential biological features related to the immaturity of their adaptive immune system, the protective effect of maternal antibodies and fetal haemoglobin. This study investigated the association between genetic variation in innate immune response genes and malaria susceptibility during the first year of life in 656 infants from a birth cohort survey performed in Nanoro, Burkina Faso. Methods Seventeen single nucleotide polymorphisms (SNPs) in 11 genes of the immune system previously associated with different malaria phenotypes were genotyped using TaqMan allelic hybridization assays in a Fluidigm platform. Plasmodium falciparum infection and clinical disease were documented by active and passive case detection. Case–control association analyses for both alleles and genotypes were carried out using univariate and multivariate logistic regression. For cytokines showing significant SNP associations in multivariate analyses, cord blood supernatant concentrations were measured by quantitative suspension array technology (Luminex). Results Genetic variants in IL-1β (rs1143634) and FcγRIIA/CD32 (rs1801274)—both in allelic, dominant and co-dominant models—were significantly associated with protection from both P. falciparum infection and clinical malaria. Furthermore, heterozygote individuals with rs1801274 SNP in FcγRIIA/CD32 showed higher IL-1RA levels compared to wild-type homozygotes (P = 0.024), a cytokine whose production is promoted by the binding of IgG immune complexes to Fcγ receptors on effector immune cells. Conclusions These findings indicate that genetic polymorphisms in genes driving innate immune responses are associated to malaria susceptibility during the first year of life, possibly by modulating production of inflammatory mediators.

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Section: Discussionmentioning

confidence: 99%

Genetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina Faso

Natama

Rovira-Vallbona

Krit

et al. 2021

Malar J

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“…Various studies in different populations revealed that patients with severe malaria-associated anemia had relatively less circulating , and patients with cerebral malaria had a higher level of 17,19), although there were reports with contradicting data (20,21). The association between IL-10 level and clinical presentation was further supported by recent findings that single-nucleotide polymorphisms of the IL-10 gene were significantly linked to malaria susceptibility or symptoms (22)(23)(24)(25). In addition, animal experiments with IL-10 knockout mouse or neutralizing anti-IL-10 antibodies proved the importance of IL-10 in controlling immunopathology in malaria (26,27).…”

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confidence: 89%

Potential Role for Regulatory B Cells as a Major Source of Interleukin-10 in Spleen from Plasmodium chabaudi-Infected Mice

et al. 2018

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Interleukin-10 (IL-10)-producing regulatory B (Breg) cells were found to be induced in a variety of infectious diseases. However, its importance in the regulation of immune response to malaria is still unclear. Here, we investigated the dynamics, phenotype, and function of Breg cells using AS-infected C57BL/6 and BALB/c mice. BALB/c mice were more susceptible to infection and had a stronger IL-10 response in spleen than C57BL/6 mice. Analysis of the surface markers of IL-10-producing cells with flow cytometry showed that CD19 B cells were one of the primary IL-10-producing populations in AS-infected C57BL/6 and BALB/c mice, especially in the latter one. The Breg cells had a heterogeneous phenotype which shifted during infection. The well-established Breg subset, CD19 CD5 CD1d cells, accounted for less than 20% of IL-10-producing B cells in both strains during the course of infection. Most Breg cells were IgG and CD138 from day 0 to day 8 postinfection. Adoptive transfer of Breg cells to C57BL/6 mice infected with AS led to a transient increase of parasitemia without an impact on survival rate. Our finding reveals that B cells play an active and important regulatory role in addition to mediating humoral immunity in immune response against malaria, which should be paid more attention in developing therapeutic or vaccine strategies against malaria involving stimulation of B cells.

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“…Immuno-genetic variants are associated with diverse degrees of malaria susceptibility, including cytokine gene polymorphisms that modify their expression and their circulating protein levels to re ect in ammatory or anti-in ammatory responses [36][37][38]. Polymorphisms in the IL-17A cytokine can impact the activity and expression of in ammatory mediators, which can affect interleukin-17 activity [39,40].…”

Section: Discussionmentioning

confidence: 99%

An elevated level of Interleukin-17A in a Senegalese malaria cohort is associated with rs8193038 IL-17A genetic variant

Thiam

Diop

COULONGES

et al. 2023

Preprint

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Malaria infection is a multifactorial disease partly modulated by host immuno-genetic factors. Recent evidence has demonstrated the importance of Interleukin-17 family proinflammatory cytokines and their genetic variants in host immunity. However, limited knowledge exists about their role in parasitic infections such as malaria. We aimed to investigate IL-17A serum levels in patients with severe and uncomplicated malaria and the gene polymorphism’s influence on the IL-17A serum levels. 125 severe (SM) and uncomplicated (UM) malaria patients and 48 free malaria controls were enrolled in this research. IL-17A serum levels were measured with ELISA. PCR and DNA sequencing were used to assess host genetic polymorphisms in IL-17A. We performed a multivariate regression to estimate the impact of human IL-17A variants on IL-17A serum level and malaria outcome. Elevated serum IL-17A levels accompanied by increased parasitemia were found in SM patients compared to UM and controls (P < 0.0001). Also, the IL-17A levels were lower in SM patients who were deceased than in those who survived. In addition, the minor allele frequencies (MAF) of two IL-17A polymorphisms (rs3819024 and rs3748067) were more prevalent in SM patients than UM patients indicating an essential role in SM. Interestingly, the heterozygous rs8193038 AG genotype was significantly associated with higher levels of IL-17A than the homozygous wild type (AA). According to our results, it can be concluded that the IL-17A gene rs8193038 polymorphism significantly affects IL-17A gene expression. Our results fill a gap in the implication of IL-17A gene polymorphisms on the cytokine level in a malaria cohort. IL-17A gene polymorphisms also may influence cytokine production in response to Plasmodium infections and may contribute to the hyperinflammatory responses during severe malaria outcomes.

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Preliminary Report on the Putative Association of Il10 -3575 T/a Genetic Polymorphism With Malaria Symptoms

Cited by 9 publications

References 40 publications

Genetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina Faso

Genetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina Faso

Potential Role for Regulatory B Cells as a Major Source of Interleukin-10 in Spleen from Plasmodium chabaudi-Infected Mice

An elevated level of Interleukin-17A in a Senegalese malaria cohort is associated with rs8193038 IL-17A genetic variant

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