Tuberculosis Progression Does Not Necessarily Equate with a Failure of Immune Control

David G Russell

doi:10.3390/microorganisms7070185

Abstract

Despite the obvious impact of tuberculosis on global health, there is currently no effective vaccine and there is increasing resistance against established front-line drug regiments. Our current understanding of disease progression in tuberculosis is shaped by data collected from the failure of immune control. We feel that this represents a biased approach, which constrains our capacity to understand both disease control and progression. In this opinion piece, we re-examine these questions in the context of recently published data from fluorescent bacterial reporter strains and the analysis of the different macrophage lineages present at sites of infection. We believe that this analysis provides alternative models for disease progression, which are not addressed through current vaccine or immune-therapeutic strategies.

Highlights

Tuberculosis is an ancient disease caused by Mycobacterium tuberculosis (Mtb) that has co-evolved with its human host since before man emerged from Africa [1,2] Ancestral strains are thought to be represented by several of the current Mtb complex strains still found in Central and West Africa, such as M. africanum
For a large part of our evolution, we have existed as small hunter/gatherer groups and it is surmised that Mtb, as an inducer of a chronic sustained infection, would have evolved to be capable of infecting many members of a group yet only generating disease in a limited set of individuals at any given time
What determines the transition from a chronic to an active state of infection? It is estimated that approximately 23% of the world’s population is infected with Mtb, but the majority harbor the pathogen in a non-active disease state, which is known as latent tuberculosis infections (LTBI) [4]

Summary

Introduction

Tuberculosis is an ancient disease caused by Mycobacterium tuberculosis (Mtb) that has co-evolved with its human host since before man emerged from Africa [1,2] Ancestral strains are thought to be represented by several of the current Mtb complex strains still found in Central and West Africa, such as M. africanum. For a large part of our evolution, we have existed as small hunter/gatherer groups and it is surmised that Mtb, as an inducer of a chronic sustained infection, would have evolved to be capable of infecting many members of a group yet only generating disease in a limited set of individuals at any given time. In this way, a human-specific pathogen lacking an animal reservoir could expand and be maintained in small population units in a relatively balanced state. Like all organisms on the planet, is driven by the “selfish gene” principle and if damaging its host comes with increased fecundity, that is the direction in which it will be selected

To Progress or Not to Progress

What Do We Know of Immune Protection?

Immune Control Is Filtered Through the Host Phagocyte

Findings

Final Comments