The Troika Host-Pathogen-Extrinsic Factors in Tuberculosis: Modulating Inflammation and Clinical Outcomes
The already enormous burden caused by tuberculosis (TB) will be further aggravated by the association of this disease with modern epidemics, as human immunodeficiency virus and diabetes. Furthermore, the increasingly aging population and the wider use of suppressive immune therapies hold the potential to enhance the incidence of TB. New preventive and therapeutic strategies based on recent advances on our understanding of TB are thus needed. In particular, understanding the intricate network of events modulating inflammation in TB will help to build more effective vaccines and host-directed therapies to stop TB. This review integrates the impact of host, pathogen, and extrinsic factors on inflammation and the almost scientifically unexplored complexity emerging from the interactions between these three factors. We highlight the exciting data showing a contribution of this troika for the clinical outcome of TB and the need of incorporating it when developing novel strategies to rewire the immune response in TB. ; HN-B acknowledges the receipt of research scholarships from Bolsa D. Manuel de Mello and the Portuguese Society for Pneumology. NO acknowledges FCT IF/00474/2014. SG is funded by the European Research Council (grant number 309540-EVODRTB); the Swiss National Science Foundation (grant number 310030_166687) SystemsX.ch. IC lab is financed by Ministerio de Economía y Competitividad (Spanish Government) research grant SAF2013-43521-R, SAF2016-77346-R, and PROMETEO/2016/122 from Generalitat Valenciana and the European Research Council (ERC) (638553-TB-ACCELERATE). The MS lab is financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). MS is an FCT Principal Investigator. Some graphical elements in the figures were designed by kjpargeter/Freepik. The funding agencies had no role in the design of the manuscript. ; Peer reviewed