PMC:3216508 / 14112-15740 JSONTXT

{"project":"2_test","denotations":[{"id":"22355539-18209095-135382467","span":{"begin":124,"end":126},"obj":"18209095"},{"id":"22355539-19864591-135382468","span":{"begin":1060,"end":1062},"obj":"19864591"},{"id":"22355539-16619290-135382469","span":{"begin":1250,"end":1252},"obj":"16619290"},{"id":"22355539-15039135-135382470","span":{"begin":1250,"end":1254},"obj":"15039135"},{"id":"22355539-18363594-135382471","span":{"begin":1307,"end":1309},"obj":"18363594"},{"id":"22355539-18209095-135382472","span":{"begin":1418,"end":1420},"obj":"18209095"},{"id":"22355539-20195465-135382473","span":{"begin":1418,"end":1422},"obj":"20195465"},{"id":"22355539-18811584-135382474","span":{"begin":1418,"end":1424},"obj":"18811584"}],"text":"Consistent with previous research that patients with tuberculosis have significantly lower Th22 response than healthy donors28, our functional assay indicated that PBMCs from individuals carrying rs2227473G allele in IL-22, which is associated with susceptibility to tuberculosis, produce significantly lower IL-22 in response to polyclonal and Mtb antigen stimulation. Although we are currently uncertain with the mechanism of predisposition to tuberculosis in individuals with the rs2227473G allele, it probably lies at the level of the macrophage as well as lung epithelial cell. The macrophage is not only the most important effector of immunity to kill infected Mycobacterium tuberculosis, but also the niche to host them. It has been well recognized that Mycobacterium tuberculosis resides in phagosomes within macrophages, and killing these mycobacteria tuberculosis requires fusion of the phagosome with a lysosome. Importantly, Dhiman et al demonstrated that human IL-22 inhibits growth of mycobacterium tuberculosis by enhancing phagolysosomal fusion10. While there is no evidence to show the effect of IL-22 on epithelial cells to kill Mycobacterium tuberculosis, IL-22 has been known to enhance lung epithelial cells to produce β-defensin1529, which is beneficial to clear infected Mycobacterium30. Besides, several studies have shown that IL-22 participates in the protective immunity against tuberculosis283132. Taken together, our findings indicate that rs2227473 polymorphism controls IL-22 response upon Mycobacterium tuberculosis infection, which in turn determines, at least in part, the outcome of infection."}