The impact of mucosal infections on acquisition and progression of tuberculosis

Abstract

More than one-third of the world's population, or over 2 billion people, are infected with Mycobacterium tuberculosis, the causative pathogen of tuberculosis in humans. Why only 10% of those infected develop active disease while the remainder harbor latent infection remains one of the greatest scientific and public health mysteries. Bacterial persistence is characterized by a dynamic state of immunological tolerance between pathogen and host. The critical role of CD4(+) T cells in defense against intracellular pathogens became evident during epidemiological studies of HIV-1 infection, which showed a clear inverse relationship between CD4(+) T-cell count in peripheral blood and increased risk of infection with M. tuberculosis, pneumocystis and Toxoplasma gondii. There is also growing evidence of a common mucosal immune system, whereby immune cells activated at one mucosal site may disseminate to remote effector sites. In this commentary, we review emerging evidence from human studies that the outcome of M. tuberculosis infection is influenced by concurrent mucosal infections, using Helicobacter pylori and geohelminths as examples. Understanding how the complexity of microbial exposures influences host immunity may have important implications for vaccine development and therapeutic interventions.

Figure 1

Hypothetical framework for interaction of protective immune responses to Mycobacterium tuberculosis (Mtb) infection in the setting of (a) H. pylori, (b) intestinal helminth, and (c) triple infection: (a) Mtb / H. pylori coinfection may enhance pro-inflammatory signals (e.g., interferon (IFN)-γ) involved in control of TB infection, ^, while (b) Mtb / helminth co-infection may suppress pro-inflammatory responses to Mtb infection via the Th2 pathway. ^, The presence of all three infections (c) would be expected to heighten pro-inflammatory and anti-inflammatory signals. Also, as shown in (d), H. pylori and helminth co-infection may suppress proinflammatory responses to H. pylori infection. ^, IL, interleukin; TNF, tumor necrosis factor.