Immunology in Tuberculosis: Challenges in Monitoring of Disease Activity and Identifying Correlates of Protection

Richard      van Altena; Sridevi      Duggirala; Matthias      I. P.Groschel; Tjip      S. van der Werf

Abstract

Humans have always lived with tubercle bacilli. Host susceptibility – both inherited and acquired – determines whether an individual infected with Mycobacterium tuberculosis will eventually fall ill and develop tuberculosis (TB). After infection with M. tuberculosis, a latent TB infection may ensue reflected by immune recognition of specific antigenic epitopes expressed by M. tuberculosis – the Region of Difference 1 proteins ESAT-6 and CFP-10 leading to interferon gamma release in vitro. Multi-Drug-Resistant TB has emerged as an enormous infectious threat in certain regions in the world, and the Acquired immunodeficiency by co-infection with HIV has accelerated the TB epidemic even further. A paradoxical response – or Immune Response Inflammatory Syndrome in the context of treatment of HIV co-infection - is an increased inflammatory reaction during effective reduction in the bacterial load. This should be differentiated from treatment failure. A huge challenge is to develop novel markers that can differentiate paradoxical responses from treatment failure. We discuss the role of protection of vaccines – especially BCG, iron metabolism and the role of vitamin D.

Keywords: Mycobacterium tuberculosis, immune response, interferon gamma, BCG, vitamin D, iron, immune response inflammatory syndrome, Multi-Drug Resistant TB (MDR-TB), sputum smear microscopy, Mycobactin