Host-directed therapies for tuberculosis: quantitative systems pharmacology approaches

Abstract

Host-directed therapies (HDTs) that modulate host-pathogen interactions offer an innovative strategy to combat Mycobacterium tuberculosis (Mtb) infections. When combined with tuberculosis (TB) antibiotics, HDTs could contribute to improving treatment outcomes, reducing treatment duration, and preventing resistance development. Translation of the interplay of host-pathogen interactions leveraged by HDTs towards therapeutic outcomes in patients is challenging. Quantitative understanding of the multifaceted nature of the host-pathogen interactions is vital to rationally design HDT strategies. Here, we (i) provide an overview of key Mtb host-pathogen interactions as basis for HDT strategies; and (ii) discuss the components and utility of quantitative systems pharmacology (QSP) models to inform HDT strategies. QSP models can be used to identify and optimize treatment targets, to facilitate preclinical to human translation, and to design combination treatment strategies.

Keywords: Mycobacterium tuberculosis; host-directed therapy; immune response; quantitative systems pharmacology.