Modeling Immune Response to Leishmania Species Indicates Adenosine As an Important Inhibitor of Th-Cell Activation

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dc.creatorHenrique de Assis Lopes Ribeiro
dc.creatorTatiani Uceli Maioli
dc.creatorLeandro Martins de Freitas
dc.creatorPaolo Tieri
dc.creatorFilippo Castiglione
dc.date.accessioned2024-03-19T14:28:27Z
dc.date.accessioned2025-09-09T00:54:35Z
dc.date.available2024-03-19T14:28:27Z
dc.date.issued2017-07-20
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.3389/fcimb.2017.00309
dc.identifier.issn2235-2988
dc.identifier.urihttps://hdl.handle.net/1843/66055
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofFrontiers in Celular and Infection Microbiology
dc.rightsAcesso Aberto
dc.subjectLeishmaniose
dc.subjectAdenosina
dc.subjectInflamação
dc.subject.otherLeishmaniasis
dc.subject.otherCutaneous
dc.subject.otherAdenosine (Ado)
dc.subject.otherModel
dc.subject.otherLattice-gas
dc.subject.otherInflammation
dc.titleModeling Immune Response to Leishmania Species Indicates Adenosine As an Important Inhibitor of Th-Cell Activation
dc.typeArtigo de periódico
local.citation.epage13
local.citation.issue309
local.citation.spage1
local.citation.volume7
local.description.resumoInfection by Leishmania protozoan parasites can cause a variety of disease outcomes in humans and other mammals, from single self-healing cutaneous lesions to a visceral dissemination of the parasite. The correlation between chronic lesions and ecto-nucleotidase enzymes activity on the surface of the parasite is addressed here using damage caused in epithelial cells by nitric oxide. In order to explore the role of purinergic metabolism in lesion formation and the outcome of the infection, we implemented a cellular automata/lattice gas model involving major immune characters (Th1 and Th2 cells, IFN-γ, IL-4, IL-12, adenosine−Ado−, NO) and parasite players for the dynamic analysis of the disease progress. The model were analyzed using partial ranking correlation coefficient (PRCC) to indicate the components that most influence the disease progression. Results show that low Ado inhibition rate over Th-cells is shared by L. major and L. braziliensis, while in L. amazonensis infection the Ado inhibition rate over Th-cells reaches 30%. IL-4 inhibition rate over Th-cell priming to Th1 independent of IL-12 are exclusive of L. major. The lesion size and progression showed agreement with published biological data and the model was able to simulate cutaneous leishmaniasis outcomes. The sensitivity analysis suggested that Ado inhibition rate over Th-cells followed by Leishmania survival probability were the most important characteristics of the process, with PRCC of 0.89 and 0.77 respectively. The simulations also showed a non-linear relationship between Ado inhibition rate over Th-cells and lesion size measured as number of dead epithelial cells. In conclusion, this model can be a useful tool for the quantitative understanding of the immune response in leishmaniasis.
local.identifier.orcidhttps://orcid.org/0000-0002-7538-3208
local.publisher.countryBrasil
local.publisher.departmentENF - DEPARTAMENTO DE NUTRIÇÃO
local.publisher.departmentENFERMAGEM - ESCOLA DE ENFERMAGEM
local.publisher.initialsUFMG
local.url.externahttps://www.frontiersin.org/articles/10.3389/fcimb.2017.00309/full

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