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Here we address the influence of specific \u2018non\u2010classical immune cells\u2019 in host responses and their effects in controlling mycobacterial growth or enabling an environment conducive for bacilli persistence. The interaction of <jats:italic>M. tuberculosis<\/jats:italic> with epithelial cells, endothelial cells, fibroblasts, adipocytes, glia and neurons and downstream cellular responses that often dictate immune regulation and disease outcome are discussed. 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