Anti-TNF immunotherapy and tuberculosis reactivation: another mechanism revealed

Abstract

Anti-TNF immunotherapy has revolutionized the treatment of some inflammatory diseases, such as RA. However, a major concern is that patients receiving this therapy have an increased risk of fungal and bacterial infection, particularly of reactivating latent tuberculosis (TB). In this issue of the JCI, in an effort to understand how anti-TNF immunotherapy affects host mechanisms required to control TB, Bruns and colleagues examined the effects of the anti-TNF therapeutic infliximab on Mycobacterium tuberculosis-specific human lymphocytes (see the related article beginning on page 1167). The authors report that a granulysin-expressing CD45RA+ subset of effector memory CD8+ T cells that contributes to the killing of intracellular M. tuberculosis is depleted in vivo by infliximab in patients with RA, and that these cells are susceptible to complement-mediated lysis in the presence of infliximab in vitro. The study provides insight into host defense mechanisms that act to control TB infection and how they are affected during anti-TNF immunotherapy for autoimmune disease.

Figure 1. Effect of TNF neutralization with infliximab on the antimycobacterial action of CD8⁺ T_EMRA cells.

In the absence of the TNF-neutralizing drug infliximab (i), cytoxic T_EMRA cells are present and release their granules containing perforin and granulysin, resulting in the death of M. tuberculosis–infected macrophages and intracellular and extracellular mycobacteria. In this issue of the JCI, Bruns et al. (3) report that in the presence of infliximab (ii), membrane TNF on T_EMRA cells is bound by the antibody, and CDC ensues. The depletion of T_EMRA cells results in suboptimal control of mycobacterial growth, leading to the potential spread of M. tuberculosis infection.