Immunotherapy for tuberculosis: future prospects

Abstract

Tuberculosis (TB) is still a major global health problem. A third of the world's population is infected with Mycobacterium tuberculosis. Only ~10% of infected individuals develop TB but there are 9 million TB cases with 1.5 million deaths annually. The standard prophylactic treatment regimens for latent TB infection take 3-9 months, and new cases of TB require at least 6 months of treatment with multiple drugs. The management of latent TB infection and TB has become more challenging because of the spread of multidrug-resistant and extremely drug-resistant TB. Intensified efforts to find new TB drugs and immunotherapies are needed. Immunotherapies could modulate the immune system in patients with latent TB infection or active disease, enabling better control of M. tuberculosis replication. This review describes several types of potential immunotherapies with a focus on those which have been tested in humans.

Keywords: HDT; immunotherapy; treatment; tuberculosis.

Figure 1

Tuberculosis (TB)-specific mucosal immune responses are important for protection against latent TB infection (LTBI) reactivation. Th1 CD4+ and Th17 CD4+ T-cells, CD8+ T-cells, γ₉δ₂ T-cells, mucosa-associated invariant T (MAIT) cells, and sIgA/IgG antibody responses are potentially protective against LTBI reactivation which could reduce both TB disease and TB transmission. Notes: All of these T-cell responses will be considered major targets for immunotherapy in this project because they can recognize intracellular Mycobacterium tuberculosis, the major pathogen reservoir during LTBI. Mucosal antibody responses also could protect against initial infection and transmission, and are being studied in other funded work by our consortium of investigators. CD4+ regulatory T-cell, T-cell exhaustion, alternatively activated macrophages unable to kill intracellular M. tuberculosis and type I IFN-induced polymorphonuclear (PMN) leukocytes can negatively regulate protective immunity in the lung.