Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics

Figure 1

Schematic representation of the immune cells involved in Mycobacterium tuberculosis infection. Distinct types of T helper (Th) cells as Th1, Th2, Th17, and regulatory T cells (Treg) are present at the site of Mycobacterium tuberculosis (MTb) infection. These cells exert their functions mainly through soluble factors. In particular, Th1 cells producing IFN-γ play an essential role in MTb clearance enhancing the macrophage microbicidal mechanisms through the activation of the iNOS pathway and the induction of phagosomes acidification, maturation, and autophagy. Moreover, tumor necrosis factor- (TNF-) α, produced by antigen presenting cells (APCs) after MTb stimulation, acts synergically with IFN-γ thus contributing to MTb control. APCs produce also interleukin- (IL-) 12 and IL-1β that are essential for resistance to MTb. Moreover, IL-23 produced by APC induces the differentiation of Th17 cells producing IL-17, IL-17F, IL-6, and TNF-α. Th17 cells are associated with MTb protection; however, when Th17 cell responses became pathogenic rather than protective, Th1 cells are induced to stop these dangerous effects. Finally, the role of Th2, Treg, and B-cell subsets in human disease still remains controversial and needs further elucidations.