Systems and Synthetic Biology

, Volume 7, Issue 4, pp 185–195

Signaling networks in Leishmania macrophages deciphered through integrated systems biology: a mathematical modeling approach

Research Article


Network of signaling proteins and functional interaction between the infected cell and the leishmanial parasite, though are not well understood, may be deciphered computationally by reconstructing the immune signaling network. As we all know signaling pathways are well-known abstractions that explain the mechanisms whereby cells respond to signals, collections of pathways form networks, and interactions between pathways in a network, known as cross-talk, enables further complex signaling behaviours. In silico perturbations can help identify sensitive crosstalk points in the network which can be pharmacologically tested. In this study, we have developed a model for immune signaling cascade in leishmaniasis and based upon the interaction analysis obtained through simulation, we have developed a model network, between four signaling pathways i.e., CD14, epidermal growth factor (EGF), tumor necrotic factor (TNF) and PI3 K mediated signaling. Principal component analysis of the signaling network showed that EGF and TNF pathways can be potent pharmacological targets to curb leishmaniasis. The approach is illustrated with a proposed workable model of epidermal growth factor receptor (EGFR) that modulates the immune response. EGFR signaling represents a critical junction between inflammation related signal and potent cell regulation machinery that modulates the expression of cytokines.


Leishmania Mathematical modeling Principal component analysis Systems biology Signaling dynamics 



Activator protein 1


Cyclic adenosine monophosphate


Cluster determinant


Complex pathway simulator


Dendritic cell


Epidermal growth factor


Epidermal growth factor receptor


Extracellular signal-regulated kinases


GTPase-activating protein


Guanosine triphosphate




IkB kinase




Integrating network objects hierarchies


IL1 receptor associated kinase


Janus kinase


Kyoto encyclopedia of genes and genomes


Kinase tyrosyl-based inhibitory motif


Leishmania major response






Mitogen-activated protein kinase


Myeloid differentiating factor


Nuclear factor κB


Natural killer cells


Nitric oxide


Ordinary differential equation


P21-activated kinase


Principal component analysis


Erythrocyte membrane protein 1


Phosphatidylinositol 3-kinase


Protein kinase A/C


Pattern-recognition receptors


System biology markup language


Protein-tyrosine phosphatase


Signal transducer and activator of transcription

TAB 1/2

TAK1 activating binding protein


TGF-β activated kinase 1


Toll-like receptors


Tumor necrotic factor alpha


Tumor necrotic factor (TNF) receptor activating factor

Supplementary material

11693_2013_9111_MOESM1_ESM.pptx (8.5 mb)
Supplementary material 1 (PPTX 8739 kb)
11693_2013_9111_MOESM2_ESM.docx (34 kb)
Supplementary material 2 (DOCX 34 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.National Centre for Cell SciencePuneIndia

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