Understanding how Mycoplasma Causes Respiratory Disease

Background

Mycoplasma is part of BRD, and mycoplasma pneumonia is responsible for 54% of feedlot mortalities in Ontario. There are no vaccines with demonstrated effectiveness against M. bovis in feedlot cattle, and there is increasing concern around antibiotic use. The tricky part is that although most feedlot cattle are infected with Mycoplasma, only a minority of them get sick from it.

This builds on earlier work where this research team found that M. bovis doesn’t cause problems on its own. At one time it was thought that immunosuppression played a role in mycoplasma pneumonia. But attempts to protect calves by stimulating the immune system ended up making them more susceptible to mycoplasma. But they also learned that if an animal had experienced inflammation due to an earlier Mannheimia infection, then a subsequent M. bovis infection caused serious trouble.

The effects of M. bovis may involve how it interacts with macrophages (white blood cells with an anti-inflammatory role that also serve as vacuum cleaners to clear pathogens and debris from the bloodstream). M. bovis can infect macrophages and hide from the immune system. It can also kill macrophages; clusters of dead macrophages in the lungs form lesions where Mycoplasma can hide from antibiotics and the immune system. Inflammation makes that worse and leads to more severe disease. So targeting inflammation may be an important part of the disease prevention strategy.

These researchers want to understand how M. bovis kills macrophages, how prior inflammation makes macrophages more susceptible to dying from M. bovis, and how different M. bovis strains differ in their ability to kill macrophages. Beyond the scope of this specific project, their ultimate long-term aspiration is to develop specific anti-inflammatory drugs that may help protect against M. bovis and a more effective vaccine.

Objectives

• Determine how M. bovis incites death of calf’s macrophages to form the characteristic caseonecrotic inflammatory lesions in the lung (infected lung looks like cheese).
• Determine how prior inflammation in the respiratory tract affects innate immune tolerance and development of harmful macrophage responses to M. bovis infection.
• Evaluate whether the above processes occur differently for disease-associated vs non-disease-associated strains of M. bovis, and the reason for those differences.

What they will do

They have developed an in vitro cell culture model where macrophages are exposed to killed Mannheimia, then to Mycoplasma. This kills the macrophages and causes lesions similar to those seen in the lung. They will do detailed studies to determine exactly how the macrophages are killed. They will examine archived calf lung samples from earlier studies to see if the same chemical signals can be found in naturally infected cattle. Then they will use the same model to study how prior inflammation (or not) leads to the lung damage seen in mycoplasma. They will also use mycoplasma isolates collected in Western Canada to try to understand why Mycoplasma from sick calves kill macrophages in vitro, while mycoplasma from healthy calves does not. The DNA of the different isolates will be sequenced to identify potential virulence antigens for vaccine development.

Implications

Mycoplasma is an ongoing concern for the feedlot sector across Canada. A better understanding of how it causes disease, and how the disease process unfolds, should help inform improved treatment and prevention strategies.