Understanding the process of Mycobacterium abscessus reinfection on host immunity
Date
2020
Authors
Ohanjanyan, Tamara, author
Ordway, Diane, advisor
Schenkel, Alan, advisor
Elf, Jessica, committee member
Chatterjee, Delphi, committee member
Journal Title
Journal ISSN
Volume Title
Abstract
Mycobacterium abscessus is a bacterial pathogen emerging in humans. The bacterium is difficult to treat, and it results in increased mortality. The patient case rates of diseases associated with this bacterium are increasing. Mycobacterium abscessus pathogenesis is poorly understood which limits our understanding of M. abscessus. The bacterium is part of the diverse family of nontuberculous mycobacterial species (NTM), and it is classified as a member of rapidly growing mycobacteria (RGM). These are environmental pathogens and they are found in tap water, showerheads, natural water sources, and soil. M. abscessus can infect individuals by breathing in aerosolized water particles, contact with surface fomites and transmission from infected patients. Individuals with human immunodeficiency syndrome (HIV) and are immunocompromised are more susceptible to infection with M. abscessus. Also, individuals with cystic fibrosis, chronic obstructive pulmonary disease or using tumor necrosis factor α (TNF- α) inhibitors are also susceptible to becoming infected with M. abscessus. Surprisingly, immunocompetent, tall slender Caucasian, non-smoking women also show an increasing rate of being infected with M. abscessus. To gain a better understanding M. abscessus pathogenesis and immune modulation, we developed βENaC over-expressing mouse models (βENaC-Tg). The main goal for this study was to discover the re-infection with the bacterium to study immune responses induced by M. abscessus. This is particularly important since the M. abscessus is an environmental pathogen and from birth to death we are all suspected to it. The reinfection process can have serious consequences in immune-compromised patients causing immune exhaustion, or in other words where the immune system is unable to fight against the bacteria after several times of infection. Our M. abscessus immunological results have shown after βENaC-Tg mice that are exposed to 4 subsequent aerosols of M. abscessus intracheal infections their CD4+ T cells show increased expression of the immune exhaustion marker PD1+ and CD11b+ macrophages show increased expression of another immune exhaustion marker CTLA4+. Together, these results support the idea that repeated environmental exposure to M. abscessus through environmental sources can potentially result in immune exhaustion leading to lack of effective function of T cells and macrophages to kill M. abscessus.