Immunological Evaluation for Personalized Interventions in Children with Tuberculosis: Should It Be Routinely Performed?

Abstract

Childhood tuberculosis (TB) is a significant public health problem and the ninth leading cause of death worldwide. Progression of Mycobacterium tuberculosis infection to active disease depends on mycobacterial virulence, environmental diversity, and host susceptibility and immune response. In children, malnutrition and immaturity of the immune system contribute to an inadequate immune response. Coinfections, though rarely described in TB, might be associated with host immune deficiencies. Here, we describe the immunological evaluation of eight pediatric patients infected with a member of the M. tuberculosis complex, most of them with concomitant pulmonary infections (bacteria, viruses, or fungi). We assessed the functionality of several innate immunity receptors, IL-12 receptor, and IFN-γ receptor, as well as the antioxidant levels (glutathione), which are essential mechanisms for fighting intracellular pathogens such as M. tuberculosis. This study is aimed at developing a thorough immunological evaluation of patients with TB and a coinfection.

Figure 1

Strategy to assess the functionality of innate and adaptive immunity. (a) Innate receptors TLR2, TLR4, TLR9, NOD1, and NOD2 were stimulated with their synthetic ligands for the production of IL-8. IFN-γ receptor was stimulated with rhIFN-γ for the production of TNF-α. (b) IL-12 receptor was stimulated with rhIL-12 for the production of IFN-γ. (c) The cellular risk for oxidative damage was determined by measuring the extracellular reduced glutathione (GSH) in plasma.

Figure 2

Graphical expression of the results of the immunological evaluation. As an aid in the interpretation of results, the graphical comparison of innate (a, b) and adaptive (c, d) responses between patient one and the mean of the control group is depicted.