Global Proteomic Analyses of Macrophage Response to Mycobacterium tuberculosis Infection

Abstract

Alveolar macrophages serve as the first line of defence against microbial infection, yet provide a unique niche for the growth of Mycobacterium tuberculosis. To better understand the evasive nature of the tubercle bacilli and its molecular manifest on the macrophage response to infection, we conducted a global quantitative proteomic profile of infected macrophages. By examining four independent controlled infection experiments, we detected 42,007 peptides resulting in the characterization of 4,868 distinct proteins. Of these, we identified 845 macrophage proteins whose expression is modulated upon infection in all replicates. We showed that the macrophages response to M. tuberculosis infection includes simultaneous and concerted upregulation of selected proteins. Using a number of statistical methods, we identified 27 proteins whose expression levels are significantly regulated outside of a 90% confidence interval about the mean. These host proteins represent the macrophage transcriptional, translational, and innate immune response to infection as well as its signaling capacity. The contribution of PtpA, an M. tuberculosis secreted virulence factor, modulated the expression levels of 11 host macrophage proteins, as categorized by RNA metabolism, translation, and cellular respiration.