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T11TS immunotherapy potentiates the repressed calcineurin-NFAT signalling pathway of T cells in Cryptococcus neoformans infected rats: a cue towards T-cell activation for antifungal immunity
S. {Omar Faruk} M., I. Hazra, S. Mondal, A. Datta, S. Moitra, P. Das K., , S. Chaudhuri
Published in
Volume: 129
Issue: 3
Pages: 753 - 767
Aims: To examine the modulation of the interacting partners of the calcineurin (CaN)-NFAT pathway in T cells during Cryptococcus neoformans fungal infection and post-T11TS immunotherapy. Methods and Results: Wistar rats were infected with C. neoformans and followed by immunotherapy with immune-potentiator T11TS. T cells were analysed by flow cytometry, immunoblotting and nuclear translocation study. The signalling proteins LCK, FYN, LAT, PLC$\gamma$1 and CaN in T cells were regulated by C. neoformans infection resulting in reduced nuclear translocation of NFAT and IL-2 expression. Following T11TS immunotherapy, the expressions of the above-mentioned proteins were boosted and thus resulting in the clearance of C. neoformans from lung and spleen. Conclusions: The precise mechanism of suppression of the T-cell function by C. neoformans is still unknown. Previously, we have shown that T11TS positively regulates the function of T cells to abrogate glioma and other immunosuppressive conditions. T11TS immunotherapy increased the expression of the above signalling partners of the CaN-NFAT pathway in T cells and improved nuclear retention of NFAT. As a result, an increased IL-2 expression leads to activation and proliferation of T cells. Significance and Impact of the Study: Our results demonstrate the role of T11TS in restoring the CaN-NFAT signalling pathway in T cells. It identifies T11TS as an immunotherapeutic agent with potential clinical outcomes to counteract C. neoformans infection.
About the journal
JournalJournal of Applied Microbiology