IL-33/ST2 Axis as a Well-Known Endogenous Defense Against Tuberculosis

Tuberculosis (TB) infection is caused by an intracellular bacterium, Mycobacterium tuberculosis (Mtb). The disease is among the most important infectious diseases, which has dedicated most cases of morbidity and mortality to itself worldwide. The global report of World Health Organization (WHO) in 2019 shows that from 10.7 million infected people in 2018, 1.6 million died. Although the BCG vaccine has been used for about a hundred years, it is only effective in children, but is not able to produce a protective and reliable immunity against adult pulmonary TB. Hence, using an alternative vaccine with high more efficacy than BCG seems to be urgent. The IL-33/ST2 axis forms of IL-33 and ST2, and both of them are the members of IL-1 family. IL-33 is secreted as an alarm in response to cell damages and cellular stress, and ST2 causes stimulation of MyD88/NF-κB signaling pathway, which is needed for the proper response of infected cells to Mtb and other intracellular pathogens. In Th2 cells, NF-κB enters into the nucleus, and acts as a transcription factor. Finally, cytokines such as IL-4, IL-5, and IL-10 are produced which are effective in the prevention of tissue damage. Based on various information, it is recommended that IL-33 can be as a novel therapeutic candidate in post-exposure cases of TB disease.