Adipose Tissue Regulates Pulmonary Pathology during TB Infection

Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, remains a major cause of mortality and morbidity worldwide. One-third of the world population is infected with M. tuberculosis, and about 15 million people with latent tuberculosis infection (LTBI) reside in the United States. An estimated 10% of individuals with LTBI are at risk of progressing to active disease. Loss of body mass, or wasting, accompanied by a significant reduction of body fat is often associated with active TB disease and is considered to be immunosuppressive and a major determinant of severity and outcome of disease. While the lungs are the primary site of M. tuberculosis infection and TB manifestation, recent reports have shown that adipose tissue serves as an important reservoir for M. tuberculosis. In this article, we investigated the association between M. tuberculosis infection, adipose tissue, and TB disease progression using a transgenic inducible “fatless” model system, the FAT-ATTAC (fat apoptosis through targeted activation of caspase 8) mouse. By selectively ablating fat tissue during M. tuberculosis infection, we directly tested the role of fat cell loss and adipose tissue physiology in regulating pulmonary pathology, bacterial burden, and immune status. Our results confirm the presence of M. tuberculosis in fat tissue after aerosol infection of mice and show that loss of fat cells is associated with an increase in pulmonary M. tuberculosis burden and pathology. We conclude that acute loss of adipose tissue during LTBI may predispose the host to active TB disease.