Isolated glycoprotein STK11 from the nutshell of Cocos nucifera L. modulated macrophage polarization to prevent the Mycobacterium tuberculosis bacilli growth in J774A.1 macrophage.

This study examines the importance of host-directed therapy against tuberculosis by targeting macrophage polarization with Cocos nucifera L. nutshell-derived STK11. RT-PCR results revealed that M2 markers (Arg1, YM-1, FIZZ1, CD206, IL-4, IL-10) were upregulated, while M1 markers (CD40, CD68, IL-6, IL-12) were downregulated in H37Ra-infected J774A.1 macrophages. Isolated glycoprotein STK11 significantly (p < 0.05) restricted the growth of Mycobacterium tuberculosis bacilli in the Middlebrook 7H9 medium and inhibited H37Ra bacilli growth within macrophages. STK11 (10 μg/ml) was also found to decrease the expression of M2 markers and increase M1 markers in infected macrophages. Simultaneously, cytokine release results claimed to upregulate the M1 related cytokines (IL-6, IL-12) and to downregulate the M2 related cytokines (IL-4, IL-10) during STK11 treated H37Ra infected macrophages. Additionally, STK11 can interact with Ras isoforms (H-Ras, N-Ras, K-Ras) in silico, the mRNA expression of K-Ras and H-Ras were found to increased, and, N-Ras was decreased in STK11-treated H37Ra-infected macrophages indicating the involvement of Ras isoforms in STK-11 treatment. Hence STK-11 might be associated with the regulation of Ras isoforms, modulating M2 to M1 repolarization in H37Ra-infected macrophages followed by restricting the M. tuberculosis bacilli growth in host macrophages.