Modeling Immune Response to Leishmania Species Indicates Adenosine As an Important Inhibitor of Th-Cell Activation
Infection by 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...
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Published in | Frontiers in cellular and infection microbiology Vol. 7; p. 309 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
20.07.2017
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Subjects | |
Online Access | Get full text |
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Summary: | Infection by
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
and
, while in
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
. 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Anton Aebischer, Robert Koch-Insitute, Germany Reviewed by: Weihuan Fang, Zhejiang University, China; Antonio M. Mendes, Instituto de Medicina Molecular (IMM), Portugal |
ISSN: | 2235-2988 2235-2988 |
DOI: | 10.3389/fcimb.2017.00309 |