Secondly, infection of Mtb activated the type 1 interferon pathway, leading to increased expression of the ISG15 conjugate system, including UBE2L6 and further leading to ISGylation of the target protein, and then, the exocrine secretion of ISG15 stimulates lymphocytes and monocytes to produce IFN‐γ. This evidence concerns the gene ISG15 and infection.