Mycobacterial Tyrosine Phosphatase PtpB Affects Host Cytokine Expression by Dephosphorylating ERK1/2 and STAT3.

Abstract

Mycobacterium tuberculosis (Mtb) tyrosine phosphatases PtpA and PtpB have been widely reported to affect host immunity response and bacterial intercellular survival. However, a comprehensive investigation into the impact of PtpA and PtpB on host phosphorylation, specifically in their roles as tyrosine phosphatases, has not yet been reported. In this study, we first conducted the potential dephosphorylation substrates map of PtpA and PtpB within the host. Our findings demonstrated that PtpB significantly decreased the phosphorylation levels of ERK1/2 and STAT3. Subsequent analysis indicated that PtpB modulated the production of cytokine TNF and IL-1β by dephosphorylating ERK1/2 and preventing its nuclear translocation. PtpB also reduced IL-6 and IL-1β expression by dephosphorylating STAT3. The in vivo experiment demonstrated increased bacterial survival and reduced cytokine expression in the PtpB-overexpression strain. Consequently, our findings demonstrate that Mtb tyrosine phosphatases PtpA and PtpB play critical roles in the global tyrosine phosphorylation landscape within the host. Specifically, PtpB modulates cytokine expression through the dephosphorylation of ERK1/2 and STAT3.