Many pathogenic bacteria have evolved sophisticated strategies, including secreting effector proteins into host cells, to subvert host innate immunity, thereby allowing them to avoid elimination and to survive within the hostile environment of host cells. The mechanisms by which specific mycobacterial effectors exploit host signaling pathways remain largely unclear. We have been investigating the molecular mechanisms underlying Mtb-host interactions. We revealed that Mtb effector proteins (such as PtpA and Mce3E) modulate host innate immunity to promote the intracellular survival of mycobacteria (Nature Immunology, 2015; The Journal of Immunology, 2015). We further found that Mtb PtpA interacts with the host ubiquitin ligase TRIM27 and antagonizes TRIM27-promoted JNK and p38 MAPK pathways activation and cell apoptosis, suggesting the existence of mutual antagonism between Mtb and host innate immune defense (Scientific Reports, 2016). More recently, we found that Mtb PtpA enters the nucleus of host cells and regulates the expression of host genes and promotes cell proliferation, providing mechanistic evidence supporting a causal link between Mtb-associated chronic infection and lung cancer development (Nature Communications, 2017). We are currently investigating the mechanism by which Mtb PtpA enter host nuclear. Collectively, Mtb secretes a variety of important 聽effector proteins (such as PtpA) to interact with multiple host proteins, signaling pathways and cellular functions to subvert host innate immunity, thus promoting its intracellular survival and cause host pathology.