Japanese researchers announce potential Johne’s breakthrough

Beef Central, 10/04/2018

JAPANESE researchers say they have unraveled the process that leads to the development of Johne’s Disease, a discovery which could lead to the development of a new method to control the disease.

Johne’s disease is a chronic wasting disease caused by the bacterium. Picture: National Agriculture and Food Research Organization.

A research team from Japan has announced it has unraveled the immunopathogenesis (the process of disease development involving an immune response) of Johne’s disease.

Researchers of Hokkaido University, the National Agriculture and Food Research Organization (NARO), and Tohoku University say they have demonstrated that a physiologically active substance called prostaglandin E2 (PGE2) impairs the immune response by up-regulating 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,” the research team said.

While Australia now uses an on-farm risk-based system to manage Johne’s Disease, Japan has a policy of control and eradication to prevent the spread of the disease.

Cattle in Japan 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.

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 up-regulation 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.”

Cattle Council of Australia Animal Health, Welfare, Biosecurity and Environment Advisor Justin Toohey told Beef Central that while it is still early days and further testing will be required, this development could potentially offer an affordable improvement on, and addition to, Australia’s current Johne’s Disease management ‘tool kit’.

He said that as Japan is committed to its program of JD eradication, findings of this nature should be considered seriously and were worth monitoring.

In Australia the Silirum vaccine is available as a control for JD in Cattle, similar to the Gudair vaccine in sheep.

Silirum’s use internationally is limited due to issues with interference with tests for tuberculosis in animals that have received it, and many countries still have bovine tuberculosis.


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