Resilience and susceptibility to paratuberculosis in sheep

Summary

Dr. De Silva from the University of Sydney explores the concepts of resilience and susceptibility in sheep exposed to Mycobacterium avium paratuberculosis (MAP), the causative agent of paratuberculosis. Through extensive experimental trials, she investigates how some animals develop clinical disease while others remain resilient, shedding light on potential biomarkers for early diagnosis. Key findings reveal that early immune responses, including interferon-gamma and antibody production, may predict resilience to the disease. Breed-specific differences in immune responses also play a crucial role. The study suggests combining diagnostic tests with gene expression analysis for improved disease management in livestock.

Takeaways

• 😀 Johne's disease is caused by *Mycobacterium avium paratuberculosis* (MAP), a slow-progressing disease with granulomatous inflammation of intestinal tissues in livestock, leading to weight loss and reduced milk yield.
• 😀 Not all animals exposed to MAP develop the disease, highlighting varying degrees of susceptibility and resilience among animals.
• 😀 Dr. De Silva's team at the University of Sydney developed an experimental model to study MAP infection in lambs, involving blood, fecal samples, and weight monitoring over extended periods.
• 😀 Infectiousness in lambs is determined by detecting viable MAP through fecal culture or observing histopathological lesions; some animals shed bacteria intermittently or remain resilient without showing disease.
• 😀 Resilience is defined as the ability to recover from infection without showing signs of disease or shedding MAP bacteria in feces by the end of the trial.
• 😀 Breeds of sheep, such as Marino and Pol Dorset, show significant differences in susceptibility to MAP, with Marino sheep being more susceptible and Pol Dorset showing higher immune responses.
• 😀 The immune response, specifically the early interferon-gamma (IFN-γ) and antibody responses, is key to understanding resilience to MAP infection.
• 😀 Early immune responses, including a spike in IFN-γ, were observed in resilient animals, suggesting their potential as early biomarkers for resilience to MAP infection.
• 😀 Gene expression analysis in lambs revealed that resilient animals had distinct patterns of gene regulation, which could help identify genetic factors associated with resilience to Johne's disease.
• 😀 Dr. De Silva emphasized the need for breed-specific considerations when diagnosing Johne's disease, especially when using diagnostic tests like antibody assays and fecal culture.
• 😀 Combining diagnostic tools, such as antibody tests and fecal culture, provides a more reliable approach to diagnosing Johne's disease, considering the intermittent shedding of MAP bacteria.

Q & A

What is Johne's disease, and what causes it?

Johne's disease, also known as paratuberculosis, is a chronic infection caused by *Mycobacterium avium paratuberculosis* (MAP). It primarily affects the intestines of ruminants, leading to weight loss and reduced milk yield.

Why is understanding resilience and susceptibility important in the context of Johne's disease?

Understanding resilience (the ability to resist infection) and susceptibility (the likelihood of developing disease after exposure) is crucial for improving diagnostic methods, vaccine development, and managing disease spread in livestock populations.

What were the main experimental trials conducted at the University of Sydney?

The main experimental trials involved exposing lambs to MAP and tracking their progression over two and a half years. The researchers observed clinical disease, immune responses, bacterial shedding, and tissue changes to understand resilience and susceptibility in the animals.

How were the lambs exposed to MAP in the trials?

Lambs were given three oral doses of MAP at around 3 to 4 months of age. Blood, fecal, and weight samples were collected regularly to monitor the disease's progression.

What is the significance of the survival curve presented in the study?

The survival curve illustrates the progression of clinical disease over time. It shows the percentage of animals that developed clinical disease or remained healthy, with different levels of infection and shedding, including persistent and transient infections.

What does the term 'resilience' mean in the context of the trials?

In this context, resilience refers to animals that were exposed to MAP but did not develop clinical disease or show any viable bacteria in their intestines at the end of the trial. These animals overcame the infection without developing symptoms.

What were the main findings regarding immune responses in resilient versus infected animals?

The study found that resilient animals had a higher early interferon-gamma response and antibody levels compared to infected animals. These early immune responses may serve as potential markers of resilience.

How did breed differences impact the disease outcomes?

The study observed differences in susceptibility between breeds. Merinos were more likely to show clinical signs of disease, while Poll Dorsets exhibited a stronger early immune response. However, no significant difference was found in bacterial shedding at the endpoint, suggesting that infectiousness may not vary greatly between breeds.

Why is interferon-gamma response important in understanding resilience?

Interferon-gamma is a key immune response that plays a role in controlling infection. A stronger early interferon-gamma response in animals is associated with better resistance to infection, making it a potential early marker for resilience in Johne's disease.

What role does gene expression play in understanding disease resilience?

Gene expression analysis identified sets of genes that were differentially regulated in resilient animals, providing insights into the molecular mechanisms that might contribute to their ability to resist disease. This could help identify biomarkers for resilience and improve diagnostic strategies.

What recommendations does Dr. de Silva make for diagnostic testing in Johne's disease?

Dr. de Silva recommends combining antibody tests with fecal culture to improve diagnostic accuracy. She also emphasizes the importance of considering the animal's age and immune response, as resilience can impact the outcome of diagnostic tests.