Investigating the role of lung inflammation during Mycobacterium avium colonisation

Popular Abstract

The call is coming from inside: your body’s own defences might be against you

Mycobacterium avium is a species of bacteria, closely related to tuberculosis, that can cause pulmonary disease in people. Despite this, we likely come in contact with these microorganisms every day. They can be found in water reservoirs and in the soil, entering the lungs of the host – like humans and rodents – through aerosolized water particles. While a healthy person’s immune system will be able to get rid of these bacteria, someone with chronic lung diseases is likely to contract an infection. In my project, I aimed to clarify the mechanisms that can decide the outcome of this interaction.

Members of the Mycobacterium genus are special. They do not fit the two major classifications for bacteria based on cell envelope structure, which presents additional challenges in treating their infections with antibiotics. A better understanding of how infection starts and eventually establishes is therefore highly relevant for providing different treatment approaches. Additionally, M. avium can grow in two distinct morphologies – called SmO or SmT (Smooth opaque or transparent) – based on their growth appearance. Previous studies found that SmT are significantly more virulent, being overrepresented in clinical cases. By studying infection in mice, our group found that only about 50% of SmT infected individuals still carry bacteria in their lungs after 24 hours. Surprisingly, we also found that for SmO this number is above 90%. Further, experiments with genetically modified mice showed that this high SmO colonisation is dependent on the host’s immune system.

When in contact with pathogens, your immune system’s first responders – white blood cells – have a variety of strategies to deal with infection. Some white blood cells can engulf pathogens in an attempt to contain them and produce chemical signals to call for help. These signals tell other immune cells where the site of infection is and mobilise them to the fight, resulting in inflammation. To study how inflammation influences bacterial colonisation, we experimented with anti-inflammatory drugs available for diverse chronic diseases treatment. We determined that the body’s natural inflammatory response and in particular one of the signalling chemicals used by immune cells – called IL-1 – are, to some degree, beneficial for bacteria. It is known that M. avium can grow inside certain immune cells. As such, the immune cell mobilisation caused by inflammation may give the bacteria more environment opportunities for growth. SmT fail to alert the immune system in the same way, which may hinder their ability to colonise the host’s lung and establish infection.

But then, how can SmT be more virulent and common in patients? We also found that SmO, despite having an initial advantage, are more easily cleared by the immune system after 2 weeks. The SmT that did manage to initially colonise the lungs, however, tend to grow in numbers over the same period. In patients with chronic pulmonary diseases, inflammation is already triggered and so SmT may benefit from this without needing to prime the response themselves. However, a lot of information about these morphologies is still missing. Further studies are needed before we can reach a clinically meaningful conclusion.

Master’s Degree Project in Molecular Biology 60 credits 2025
Department of Biology, Lund University

Advisor: Fredric Carlsson and Julia Lienard
Department of Biology, Evolutionary Ecology and Infection Biology unit

• author: Janeiro Sequeira, Rodrigo Miguel
• supervisor: Fredric Carlsson; Julia Lienard
• organization: Degree Projects in Molecular Biology
• course: MOBN03 20242
• year: 2025
• type: H2 - Master's Degree (Two Years)
• subject: Biology and Life Sciences
• language: English
• id: 9214798
• date added to LUP: 2025-11-03 13:41:23
• date last changed: 2025-11-03 13:41:23