期刊
MOLECULES
卷 27, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/molecules27010124
关键词
IL6; SOCS1; SOCS3; systems biology; synthetic biology; leishmaniasis
资金
- Department of Biotechnology, Ministry of Science and Technology, Government of India
Macrophage phenotype plays a crucial role in the pathogenesis of Leishmanial infection, and the expression levels of cytokine signaling suppressors (SOCS) in correlation with the establishment of infection are not well understood. IL6 induces the expression of SOCS1 and SOCS3 through JAK-STAT signaling, and the immunological crosstalk between TLR2 and IL6 signaling pathways is established during the early stage of Leishmania major infection. Synthetic biology approaches can be used to target the activity of SOCS1 and restore pro-inflammatory cytokine expression during infection.
Macrophage phenotype plays a crucial role in the pathogenesis of Leishmanial infection. Pro-inflammatory cytokines signals through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway that functions in parasite killing. Suppression of cytokine signaling (SOCS) is a well-known negative feedback regulator of the JAK/STAT pathway. However, change in the expression levels of SOCSs in correlation with the establishment of infection is not well understood. IL6 is a pleotropic cytokine that induces SOCS1 and SOCS3 expression through JAK-STAT signaling. Mathematical modeling of the TLR2 and IL6 signaling pathway has established the immune axis of SOCS1 and SOCS3 functioning in macrophage polarization during the early stage of Leishmania major infection. The ratio has been quantified both in silico and in vitro as 3:2 which is required to establish infection during the early stage. Furthermore, phosphorylated STAT1 and STAT3 have been established as an immunological cross talk between TLR2 and IL6 signaling pathways. Using synthetic biology approaches, peptide based immuno-regulatory circuits have been designed to target the activity of SOCS1 which can restore pro-inflammatory cytokine expression during infection. In a nutshell, we explored the potential of synthetic biology to address and rewire the immune response from Th2 to Th1 type during the early stage of leishmanial infection governed by SOCS1/SOCS3 immune axis.
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