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Macrophages are primary host of Mycobacterium tuberculosis (M.tb) and the central effector of in vivo innate immune responses against bacteria.Though the interaction between macrophages and mycobacteria has been widely investigated,the molecular mechanisms of M.tb pathogenesis in macrophages are still not clear.In this work,we investigated the altered protein expression profiles of macrophages after virulent H37Rv strain and avirulent H37Ra strain infection by tandem mass tag-based quantitative proteomics.Among 6762 identified proteins of macrophages,the expression levels of 235 proteins were significantly altered,which is supposed to be related to the infection of different strains.By bioinformatics analysis at systems level,we found that these proteins are mainly involved in the biological process of apoptosis,blood coagulation,oxidative phosphorylation,and others.The enormous variation in protein profiles between macrophages infected with H37Ra and H37Rv suggests the existence of four different immunity mechanisms that decide the fates of macrophages and M.tb.These data may provide a better understanding of M.tb pathogenesis within the host,which contributes to the prevention and clinical treatment of tuberculosis.