Genetic variation of FcγRIIa induces higher uptake of Leishmania infantum and modulates cytokine production by adherent mononuclear cells in vitro
IntroductionSingle nucleotide variations (SNVs) are specific genetic variations that commonly occur in a population and often do not manifest phenotypically. However, depending on their location and the type of nucleotide exchanged, an SNV can alter or inhibit the function of the gene in which it oc...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1343602/full |
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| author | Jonatas da Silva Catarino Rafael Faria de Oliveira Marcos Vinicius Silva Helioswilton Sales-Campos Helioswilton Sales-Campos Fernanda Bernadelli de Vito Djalma Alexandre Alves da Silva Lucila Langoni Naves Carlo José Freire Oliveira Denise Bertulucci Rocha Rodrigues Virmondes Rodrigues Virmondes Rodrigues |
| author_facet | Jonatas da Silva Catarino Rafael Faria de Oliveira Marcos Vinicius Silva Helioswilton Sales-Campos Helioswilton Sales-Campos Fernanda Bernadelli de Vito Djalma Alexandre Alves da Silva Lucila Langoni Naves Carlo José Freire Oliveira Denise Bertulucci Rocha Rodrigues Virmondes Rodrigues Virmondes Rodrigues |
| author_sort | Jonatas da Silva Catarino |
| collection | DOAJ |
| description | IntroductionSingle nucleotide variations (SNVs) are specific genetic variations that commonly occur in a population and often do not manifest phenotypically. However, depending on their location and the type of nucleotide exchanged, an SNV can alter or inhibit the function of the gene in which it occurs. Immunoglobulin G (IgG) receptor genes have exhibited several polymorphisms, including rs1801274, which is found in the FcgRIIa gene. The replacement of A with T results in a Histidine (H) to Arginine (R) substitution, altering the affinity of the IgG receptor for IgG subtypes and C-reactive protein (CRP). In this study, we analyzed rs1801274 and its functional implications concerning L. Infantum uptake and cytokine production.MethodsWe genotyped 201 individuals from an endemic area for visceral leishmaniasis to assess the presence of rs1801274 using Taqman probes for a candidate gene study. Additionally, we included seventy individuals from a non-endemic area for a functional study. Subsequently, we isolated and cultivated one-week adherent mononuclear cells (AMCs) derived from the peripheral blood of participants residing in the non-endemic region in the presence of L. infantum promastigotes, with and without antigen-specific IgG and/or CRP. We analyzed the rate of phagocytosis and the production of nitric oxide (NO), tumor necrosis factor (TNF)-a, interleukin (IL)-10, IL-12 p70, IL-1b, IL- 6, and IL-8 in the culture supernatants.Results and discussionIn participants from the endemic region, the A/G (H/R isoform) heterozygous genotype was significantly associated with susceptibility to the disease. Furthermore, SNVs induced a change in the phagocytosis rate in an opsonin-dependent manner. Opsonization with IgG increased the production of IL-10, TNF-a, and IL-6 in AMCs with the H/R isoform, followed by a decrease in NO production. The results presented here suggest that the rs1801274 polymorphism is linked to a higher susceptibility to visceral leishmaniasis. |
| first_indexed | 2024-03-07T23:07:20Z |
| format | Article |
| id | doaj.art-a584f5ca1f994e6f8bfa2e85223f989f |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-07T23:07:20Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-a584f5ca1f994e6f8bfa2e85223f989f2024-02-22T04:39:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.13436021343602Genetic variation of FcγRIIa induces higher uptake of Leishmania infantum and modulates cytokine production by adherent mononuclear cells in vitroJonatas da Silva Catarino0Rafael Faria de Oliveira1Marcos Vinicius Silva2Helioswilton Sales-Campos3Helioswilton Sales-Campos4Fernanda Bernadelli de Vito5Djalma Alexandre Alves da Silva6Lucila Langoni Naves7Carlo José Freire Oliveira8Denise Bertulucci Rocha Rodrigues9Virmondes Rodrigues10Virmondes Rodrigues11Laboratory of Immunology, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, BrazilLaboratory of Immunology, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, BrazilLaboratory of Immunology, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, BrazilLaboratory of Immunology, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, BrazilInstitute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, GO, BrazilLaboratory of Immunology, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, BrazilLaboratory of Immunology, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, BrazilLaboratory of Immunology, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, BrazilLaboratory of Immunology, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, BrazilLaboratory of Immunology, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, BrazilLaboratory of Immunology, Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, BrazilNational Institute of Neuroimmuno Modulation, Rio de Janeiro, BrazilIntroductionSingle nucleotide variations (SNVs) are specific genetic variations that commonly occur in a population and often do not manifest phenotypically. However, depending on their location and the type of nucleotide exchanged, an SNV can alter or inhibit the function of the gene in which it occurs. Immunoglobulin G (IgG) receptor genes have exhibited several polymorphisms, including rs1801274, which is found in the FcgRIIa gene. The replacement of A with T results in a Histidine (H) to Arginine (R) substitution, altering the affinity of the IgG receptor for IgG subtypes and C-reactive protein (CRP). In this study, we analyzed rs1801274 and its functional implications concerning L. Infantum uptake and cytokine production.MethodsWe genotyped 201 individuals from an endemic area for visceral leishmaniasis to assess the presence of rs1801274 using Taqman probes for a candidate gene study. Additionally, we included seventy individuals from a non-endemic area for a functional study. Subsequently, we isolated and cultivated one-week adherent mononuclear cells (AMCs) derived from the peripheral blood of participants residing in the non-endemic region in the presence of L. infantum promastigotes, with and without antigen-specific IgG and/or CRP. We analyzed the rate of phagocytosis and the production of nitric oxide (NO), tumor necrosis factor (TNF)-a, interleukin (IL)-10, IL-12 p70, IL-1b, IL- 6, and IL-8 in the culture supernatants.Results and discussionIn participants from the endemic region, the A/G (H/R isoform) heterozygous genotype was significantly associated with susceptibility to the disease. Furthermore, SNVs induced a change in the phagocytosis rate in an opsonin-dependent manner. Opsonization with IgG increased the production of IL-10, TNF-a, and IL-6 in AMCs with the H/R isoform, followed by a decrease in NO production. The results presented here suggest that the rs1801274 polymorphism is linked to a higher susceptibility to visceral leishmaniasis.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1343602/fullleishmaniasisFcγRIIa (CD32a)polymorphismAMCsinfectionphagocytosis |
| spellingShingle | Jonatas da Silva Catarino Rafael Faria de Oliveira Marcos Vinicius Silva Helioswilton Sales-Campos Helioswilton Sales-Campos Fernanda Bernadelli de Vito Djalma Alexandre Alves da Silva Lucila Langoni Naves Carlo José Freire Oliveira Denise Bertulucci Rocha Rodrigues Virmondes Rodrigues Virmondes Rodrigues Genetic variation of FcγRIIa induces higher uptake of Leishmania infantum and modulates cytokine production by adherent mononuclear cells in vitro Frontiers in Immunology leishmaniasis FcγRIIa (CD32a) polymorphism AMCs infection phagocytosis |
| title | Genetic variation of FcγRIIa induces higher uptake of Leishmania infantum and modulates cytokine production by adherent mononuclear cells in vitro |
| title_full | Genetic variation of FcγRIIa induces higher uptake of Leishmania infantum and modulates cytokine production by adherent mononuclear cells in vitro |
| title_fullStr | Genetic variation of FcγRIIa induces higher uptake of Leishmania infantum and modulates cytokine production by adherent mononuclear cells in vitro |
| title_full_unstemmed | Genetic variation of FcγRIIa induces higher uptake of Leishmania infantum and modulates cytokine production by adherent mononuclear cells in vitro |
| title_short | Genetic variation of FcγRIIa induces higher uptake of Leishmania infantum and modulates cytokine production by adherent mononuclear cells in vitro |
| title_sort | genetic variation of fcγriia induces higher uptake of leishmania infantum and modulates cytokine production by adherent mononuclear cells in vitro |
| topic | leishmaniasis FcγRIIa (CD32a) polymorphism AMCs infection phagocytosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1343602/full |
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