APOL1 expression is induced by Trypanosoma brucei gambiense infection but is not associated with differential susceptibility to sleeping sickness

Ilboudo, Hamidou; Berthier, David; Camara, Mamadou; Camara, Oumou; Kaboré, Jacques; Léno, Mamadou; Keletigui, Sow; Chantal, Isabelle; Jamonneau, Vincent; Bélem, Adrien Marie Gaston; Cuny, G; Bucheton, Bruno

doi:10.1016/j.meegid.2012.05.010

Cited by 17 publications

(16 citation statements)

References 26 publications

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“…The second group, (SERO TL+/CATTneg) comprised 15 individuals in whom trypanosomes were never detected but who displayed decreasing CATT responses (with end titer becoming <1/8). Similarly decreasing CATT responses were also observed in treated HAT patients in Guinea [19]; they were also observed in confirmed HAT patients refusing treatment in Côte d'Ivoire and in whom parasitological testing became subsequently negative [4], suggesting that these SERO TL+ subjects were engaged in a process of self-cure. The third group (SERO TL+/CATT≥1/8) was composed of 13 individuals who maintained elevated CATT responses throughout the follow-up period and who can be considered as asymptomatic carriers of parasite with parasitemia below the detection limit of parasitological tests.…”

Section: Resultssupporting

confidence: 53%

Unravelling Human Trypanotolerance: IL8 is Associated with Infection Control whereas IL10 and TNFα Are Associated with Subsequent Disease Development

et al. 2014

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In West Africa, Trypanosoma brucei gambiense, causing human African trypanosomiasis (HAT), is associated with a great diversity of infection outcomes. In addition to patients who can be diagnosed in the early hemolymphatic phase (stage 1) or meningoencephalitic phase (stage 2), a number of individuals can mount long-lasting specific serological responses while the results of microscopic investigations are negative (SERO TL+). Evidence is now increasing to indicate that these are asymptomatic subjects with low-grade parasitemia. The goal of our study was to investigate the type of immune response occurring in these “trypanotolerant” subjects. Cytokines levels were measured in healthy endemic controls (n = 40), stage 1 (n = 10), early stage 2 (n = 19), and late stage 2 patients (n = 23) and in a cohort of SERO TL+ individuals (n = 60) who were followed up for two years to assess the evolution of their parasitological and serological status. In contrast to HAT patients which T-cell responses appeared to be activated with increased levels of IL2, IL4, and IL10, SERO TL+ exhibited high levels of proinflammatory cytokines (IL6, IL8 and TNFα) and an almost absence of IL12p70. In SERO TL+, high levels of IL10 and low levels of TNFα were associated with an increased risk of developing HAT whereas high levels of IL8 predicted that serology would become negative. Further studies using high throughput technologies, hopefully will provide a more detailed view of the critical molecules or pathways underlying the trypanotolerant phenotype.

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Section: Resultssupporting

confidence: 53%

Unravelling Human Trypanotolerance: IL8 is Associated with Infection Control whereas IL10 and TNFα Are Associated with Subsequent Disease Development

et al. 2014

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“…b . gambiense infection but not associated with differential susceptibility to sleeping sickness [ 21 ]. APOL1 rs73885319 is also known as the G1 allele of APOL1 and is associated with kidney disease in African Americans and the relatively high frequency of this deleterious allele was assumed to be due to selection by HAT [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…b . gambiense infection but expression is not associated with susceptibility to sleeping sickness [ 21 ]. MIF contributes to inflammation-associated pathology in the chronic phase of T .…”

Section: Introductionmentioning

confidence: 99%

Candidate genes-based investigation of susceptibility to Human African Trypanosomiasis in Côte d’Ivoire

et al. 2017

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Human African Trypanosomiasis (HAT) or sleeping sickness is a Neglected Tropical Disease. Long regarded as an invariably fatal disease, there is increasing evidence that infection by T. b. gambiense can result in a wide range of clinical outcomes, including latent infections, which are long lasting infections with no parasites detectable by microscopy. The determinants of this clinical diversity are not well understood but could be due in part to parasite or host genetic diversity in multiple genes, or their interactions. A candidate gene association study was conducted in Côte d’Ivoire using a case-control design which included a total of 233 subjects (100 active HAT cases, 100 controls and 33 latent infections). All three possible pairwise comparisons between the three phenotypes were tested using 96 SNPs in16 candidate genes (IL1, IL4, IL4R, IL6, IL8, IL10, IL12, IL12R, TNFA, INFG, MIF, APOL1, HPR, CFH, HLA-A and HLA-G). Data from 77 SNPs passed quality control. There were suggestive associations at three loci in IL6 and TNFA in the comparison between active cases and controls, one SNP in each of APOL1, MIF and IL6 in the comparison between latent infections and active cases and seven SNP in IL4, HLA-G and TNFA between latent infections and controls. No associations remained significant after Bonferroni correction, but the Benjamini Hochberg false discovery rate test indicated that there were strong probabilities that at least some of the associations were genuine. The excess of associations with latent infections despite the small number of samples available suggests that these subjects form a distinct genetic cluster different from active HAT cases and controls, although no clustering by phenotype was observed by principle component analysis. This underlines the complexity of the interactions existing between host genetic polymorphisms and parasite diversity.

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“…The Bambuti people of the Mbomo region in the Democratic Republic of the Congo have long been believed to be less susceptible to African sleeping sickness (Frezil, 1983 ), although no controlled study has been performed to test this assumption or investigate their APOL1 alleles. It is also becoming increasingly apparent that infection by T. b. gambiense is not always fatal with the recent identification of asymptomatic and self-cure cases from Côte d'Ivoire (Ilboudo et al 2012 ; Jamonneau et al 2012 ). The APOL1 sequences from these individuals have not been assessed, although a recent study assessing APOL1 selection across Africa has identified an allele termed G3 that is under selection in the Fulani people of Cameroon, a region affected by T. b. gambiense African sleeping sickness (Ko et al 2013 ).…”

Section: Evolving Primate Resistance To T B Rhodesiense mentioning

confidence: 99%

A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome

et al. 2014

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SUMMARYTrypanosoma brucei is the causative agent of African sleeping sickness in humans and one of several pathogens that cause the related veterinary disease Nagana. A complex co-evolution has occurred between these parasites and primates that led to the emergence of trypanosome-specific defences and counter-measures. The first line of defence in humans and several other catarrhine primates is the trypanolytic protein apolipoprotein-L1 (APOL1) found within two serum protein complexes, trypanosome lytic factor 1 and 2 (TLF-1 and TLF-2). Two sub-species of T. brucei have evolved specific mechanisms to overcome this innate resistance, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. In T. b. rhodesiense, the presence of the serum resistance associated (SRA) gene, a truncated variable surface glycoprotein (VSG), is sufficient to confer resistance to lysis. The resistance mechanism of T. b. gambiense is more complex, involving multiple components: reduction in binding affinity of a receptor for TLF, increased cysteine protease activity and the presence of the truncated VSG, T. b. gambiense-specific glycoprotein (TgsGP). In a striking example of co-evolution, evidence is emerging that primates are responding to challenge by T. b. gambiense and T. b. rhodesiense, with several populations of humans and primates displaying resistance to infection by these two sub-species.

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APOL1 expression is induced by Trypanosoma brucei gambiense infection but is not associated with differential susceptibility to sleeping sickness

Cited by 17 publications

References 26 publications

Unravelling Human Trypanotolerance: IL8 is Associated with Infection Control whereas IL10 and TNFα Are Associated with Subsequent Disease Development

Unravelling Human Trypanotolerance: IL8 is Associated with Infection Control whereas IL10 and TNFα Are Associated with Subsequent Disease Development

Candidate genes-based investigation of susceptibility to Human African Trypanosomiasis in Côte d’Ivoire

A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome

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