Mycobacterium tuberculosis: An Adaptable Pathogen Associated With Multiple Human Diseases

Abstract

Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), is an extremely successful pathogen that adapts to survive within the host. During the latency phase of infection, M. tuberculosis employs a range of effector proteins to be cloud the host immune system and shapes its lifestyle to reside in granulomas, sophisticated, and organized structures of immune cells that are established by the host in response to persistent infection. While normally being restrained in immunocompetent hosts, M. tuberculosis within granulomas can cause the recrudescence of TB when host immunity is compromised. Aside from causing TB, accumulating evidence suggests that M. tuberculosis is also associated with multiple other human diseases, such as pulmonary complications, autoimmune diseases, and metabolic syndromes. Furthermore, it has been recently appreciated that M. tuberculosis infection can also reciprocally interact with the human microbiome, which has a strong link to immune balance and health. In this review, we highlight the adaptive survival of M. tuberculosis within the host and provide an overview for regulatory mechanisms underlying interactions between M. tuberculosis infection and multiple important human diseases. A better understanding of how M. tuberculosis regulates the host immune system to cause TB and reciprocally regulates other human diseases is critical for developing rational treatments to better control TB and help alleviate its associated comorbidities.

A Mycobacterium tuberculosis surface protein recruits ubiquitin to trigger host xenophagy

“…Initially, it seems counterintuitive that Mtb would retain such a conserved UBA domain-containing protein like Rv1468c that functions to mark bacteria for host clearance and thus avoiding excessive host inflammation. In fact, the long-term intimate interplays between Mtb and the host are quite nuanced, rather than irreconcilably in conflict until one is defeated 47 . In about 90% of the infected individuals, Mtb could persist in the host by establishing a latent state instead of causing host severe inflammatory responses and tissue damage, as many severe and acute infection-causing pathogens normally do 48 .…”

Targeting Macrophages: Friends or Foes in Disease?

“…This provides an environment in which the pathogen is hidden from the immune system and allows it to replicate. Diseases with this type of behavior include tuberculosis (caused by Mycobacterium tuberculosis) and leishmaniasis (caused by Leishmania species) (Chai et al, 2018; Rossi and Fasel, 2018). In order to minimize the possibility of becoming the host of an intracellular bacteria, macrophages have evolved defense mechanisms such as induction of nitric oxide and reactive oxygen intermediates, which are toxic to microbes, restrict the microbe’s nutrient supply, and induce autophagy (Weiss and Schaible, 2015).…”

Lung gene expression signatures suggest pathogenic links and molecular markers for pulmonary tuberculosis, adenocarcinoma and sarcoidosis

“…Mtb is a paradigmatic intracellular pathogen that can persist in the lung and interact with host cells for a long term, leading to a range of pathological outcomes 2,3 . TB infection has long been associated with multiple other lung diseases, including lung cancer and sarcoidosis [4][5][6] . Internationally, lung cancer is the leading cause of cancer-related death in humans, among which lung adenocarcinoma (LUAD) is the most common histologic subtype 7 .…”