Unraveling the immunopathogenesis of Johne's disease

April 02, 2018

A research team has unraveled the immunopathogenesis of Johne's disease, a chronic bovine disease that has caused endemics in Japan and many other countries, placing financial burdens on cattle farmers.

Researchers of Hokkaido University, the National Agriculture and Food Research Organization (NARO), and Tohoku University demonstrated that a physiologically active substance called prostaglandin E2 (PGE2) impairs the immune response by upregulating the expression of an immunoinhibitory molecule, programmed death-ligand 1 (PD-L1), in cattle affected with Johne's disease. The discovery is expected to help develop a method to control Johne's disease, which is most frequently reported among legally designated infectious bovine diseases in Japan.

Johne's disease is a type of chronic enteritis caused by Mycobacterium avium subsp. paratuberculosis, leading to diarrhea and weight loss in cattle, and occasionally death. This disease has led to endemics in Japan and 816 clinical cases were reported in 2017. Cattle diagnosed with the disease must be culled to prevent its spread. Cattle farmers are also required to give regular check-ups to all other cattle at the same farm for a certain period, disinfect their cattle barns and are not allowed to move animals out of the farm freely. There has been no effective method to prevent the spread of the disease, including vaccination.

The researchers investigated the immunosuppressive effects of PGE2, which is known to appear in increased amounts in cattle with Johne's disease. Their experiments showed PGE2 has immunosuppressive effects on T-cell, a type of lymphocyte that plays an important role in the immune system. PGE2 also induced the upregulation of PD-L1, a immunosuppressive molecule, in immune cells isolated from cows. The researchers also found PGE2 and PD-L1 were co-expressed in intestinal lesions of the infected cattle.

In addition, they found that the inhibition of cyclooxygenase-2 (COX-2), which is involved in the synthesis of PGE2, boosted immune response to the mycobacteria causing Johne's disease. When COX-2 inhibitor is combined with anti-PD-L1 blocking antibodies, it further enhances the immune response to the mycobacteria.

"Our data suggests that immunosuppressive effects of PGE2 are strongly connected to the progression of Johne's disease," says Associate Professor Satoru Konnai of the research team at Hokkaido University. "We plan to conduct clinical trials to verify how the COX-2 inhibitor and anti-PD-L1 antibodies boost immune responses in cattle with Johne's disease, in addition to examining the roles of PGE2 in cattle afflicted with other diseases."
-end-


Hokkaido University

Related Immune Response Articles from Brightsurf:

Boosting chickens' own immune response could curb disease
Broiler chicken producers the world over are all too familiar with coccidiosis, a parasite-borne intestinal disease that stalls growth and winnows flocks.

Cells sacrifice themselves to boost immune response to viruses
Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection.

Children's immune response more effective against COVID-19
Children and adults exhibit distinct immune system responses to infection by the virus that causes COVID-19, a finding that helps explain why COVID-19 outcomes tend to be much worse in adults, researchers from Yale and Albert Einstein College of Medicine report Sept.

Which immune response could cause a vaccine against COVID-19?
Immune reactions caused by vaccination can help protect the organism, or sometimes may aggravate the condition.

Obesity may alter immune system response to COVID-19
Obesity may cause a hyperactive immune system response to COVID-19 infection that makes it difficult to fight off the virus, according to a new manuscript published in the Endocrine Society's journal, Endocrinology.

Immune response to Sars-Cov-2 following organ transplantation
Even patients with suppressed immune systems can achieve a strong immune response to Sars-Cov-2.

'Relaxed' T cells critical to immune response
Rice University researchers model the role of relaxation time as T cells bind to invaders or imposters, and how their ability to differentiate between the two triggers the body's immune system.

A novel mechanism that triggers a cellular immune response
Researchers at Baylor College of Medicine present comprehensive evidence that supports a novel trigger for a cell-mediated response and propose a mechanism for its action.

Platelets exacerbate immune response
Platelets not only play a key role in blood clotting, but can also significantly intensify inflammatory processes.

How to boost immune response to vaccines in older people
Identifying interventions that improve vaccine efficacy in older persons is vital to deliver healthy ageing for an ageing population.

Read More: Immune Response News and Immune Response Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.