Cattle: Unravelling the immunopathogenesis of Johne’s disease

A Japanese research team has unravelled the immunopathogenesis of Johne’s disease, a chronic bovine disease that has caused endemics in many countries and placed financial burdens on cattle farmers.

Researchers of Japan’s Hokkaido University, the National Agriculture and Food Research Organization, 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.

The team plans 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 and ti examine the roles of PGE2 in cattle afflicted with other diseases.

Journal Reference:

Yamato Sajiki, Satoru Konnai, Tomohiro Okagawa, Asami Nishimori, Naoya Maekawa, Shinya Goto, Ryoyo Ikebuchi, Reiko Nagata, Satoko Kawaji, Yumiko Kagawa, Shinji Yamada, Yukinari Kato, Chie Nakajima, Yasuhiko Suzuki, Shiro Murata, Yasuyuki Mori, Kazuhiko Ohashi. Prostaglandin E2 induction suppresses the Th1 immune responses in cattle with Johne’s disease. Infection and Immunity, 2018; IAI.00910-17 DOI: 10.1128/IAI.00910-17

Source: ScienceDaily

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Ministry for Primary Industries is supporting World Antibiotics Awareness Week

The Ministry for Primary Industries is supporting the theme of this year’s World Antibiotic Awareness Week: “Seek advice from a qualified health care professional before taking antibiotics.”

Research shows that the global growth of antimicrobial resistance is undermining the effectiveness of antibiotics.

“Antibiotics are important for treating bacterial infections in humans and animals but we need to make sure they are used appropriately,” says the ministry’s Director Systems Audit, Assurance and Monitoring, Allan Kinsella.

“Animals sometimes need antibiotics to treat bacterial infections. All antibiotics registered for use in animals in New Zealand are rigorously assessed before being used,” says Mr Kinsella.

Most antibiotics can be used only to treat individual animals or groups of animals that show symptoms of disease or prevent sickness in cases where there’s a high risk to the animal.

“New Zealand is a low user of antibiotics in food producing animals compared to many other countries,” Mr Kinsella said.

“However, we need to remain vigilant. Any animal owner who thinks their animal should be treated with antibiotics should discuss this with their vet.”

This year New Zealand began implementing its five-year Antimicrobial Resistance Action Plan to minimise the impact of antimicrobial resistance to human, animal and plant health.

The plan’s activities cover 5 different areas: awareness and understanding; surveillance and research; infection prevention and control; antimicrobial stewardship; and governance, collaboration and investment.

The Ministry for Primary Industries is working with the Ministry of Health and a wide range of groups and organisations to try to ensure New Zealand is on the right track. The five-year plan builds on previous work undertaken by the ministry to manage antimicrobial resistance in animals.

Mr Kinsella says tNew Zealand has a robust regulatory framework for managing antibiotics and other veterinary medicines.

“MPI must be satisfied that all antibiotics approved for use in animals are appropriate to the animal and do not harm human health.”

You can learn HERE how antibiotic use is controlled in NZ

Benefits of pre-lamb drenching come under the AgResearch spotlight

The latest research is challenging the popular belief that drenching ewes around lambing time will consistently provide production and financial benefit.

At the recent Beef + Lamb New Zealand AgInnovation conference in Palmerston North, AgResearch parasitologist Dr Dave Leathwick reviewed the science around the production benefits from drenching ewes at lambing. This showed some new data on the benefits of focusing drench treatments on ewes with low body condition scores.

One common theme emerged from the  review of all on-farm trials conducted in New Zealand since the 1960s – there is no consistent production benefit from drenching ewes around lambing time, whether farmers use an oral drench, a long-acting injection or a capsule.

This means that sometimes there is a measurable benefit and sometimes there isn’t, Leathwick says in a media statement (HERE).

“But it’s a bit more complicated than that, because many of the trials didn’t actually measure all the variables necessary to make a proper decision on the benefits of treatment.”

“This was clearly seen in the recent series of trials conducted by farmers in the Wairarapa, the ‘Wairarapa Anthelmintic Trial’.

This study was largely run by farmers and was funded by a complex of industry agencies and companies. It was by far the most comprehensive study ever conducted in New Zealand on this topic.

“The key outcome from this work was that in nearly 50 per cent of the trials, there was a net financial loss as a result of drenching ewes. This came about because while treated ewes and their lambs tended to be heavier at weaning, there tended to be fewer of them ie. ewes treated with long-acting drenches, on average, weaned fewer lambs.

“The fewer lambs effectively cancelled out any benefit from the heavier ewes and lambs. Further, the financial analysis showed that the biggest driver of dollar return on investment, was, in fact, the number of lambs weaned, rather than ewe or lamb weaning weights. The results showed the biggest driver of financial benefit was lamb survival.”

An unexpected result from the Wairarapa study was that the response to treatment was independent of ewe body condition score pre-lambing. In other words, all ewes responded the same regardless of their condition.

AgResearch scientists have been following up on this finding over the past year and have further analysed data from both the Wairarapa study and other trials. Their recent findings show that over the period from pre-lambing to weaning, some ewes increase in condition, some lose condition and some stay the same.

“The proportions following this pattern are exactly the same whether the ewes were drenched or not, and the type of drench was irrelevant,” Dr Leathwick says.

“We interpret these data as telling us that low body condition in ewes at this time of year is unlikely to be caused by worms. Even when skinny ewes are given a long-acting drench, many of them don’t improve in condition, and some lose condition.”

The message seems to be that ill-thrift in ewes is probably due to other factors.

Work from Massey University has suggested subclinical pneumonia and facial eczema are more likely to be involved. While the causes of ill-thrift remain uncertain, it seems worms are not important.

“So, if you try and solve an ill-thrift problem in your ewes by drenching you will probably fail.

“Therefore, while farmers may, in some situations, see some benefit from drenching ewes around lambing, they should be cautious, as a positive financial benefit is not certain. The benefits of treating ewes pre-lambing are not at all reliable or consistent, and there may be much better ways to spend your money.”

The best advice for maximising kg lambs weaned/ewe mated, Leathwick says, seems to be to get as many ewes as possible to condition score 3 before lambing starts.

Researchers work on next-generation sanitisers to control bovine mastitis

Researchers from the Universities of Otago and Auckland have teamed up with Deosan, the manufacturer and supplier of a range of animal health products, to develop new sanitisers for mastitis management. The aim is to enhance New Zealand’s position as a global leader in milk quality by improving performance in mastitis prevention and guard against the emergence of antimicrobial resistance.

Mastitis, a bacterial infection of the udder, is the foremost production-limiting disease for dairying worldwide. It costs the New Zealand dairy industry more than $280 million a year in treatment and discarded milk.

The industry  relies largely on just two antimicrobial sanitisers to control mastitis, administered through teat sprays. Both formulations contain bioactive ingredients (chlorhexidine or iodine) that are also widely used for infection control in hospitals.

The mounting threat of antimicrobial resistance in clinical environments and lower acceptance of chemical residues in consumer products have prompted calls for the development of new types of products for use within the dairy industry.

Previous research by the team (supported by Agmardt) has uncovered a new class of molecules with  potent antimicrobial activity against mastitis-causing microorganisms. These have the potential to synergise with current treatments while being harmless to mammalian cells.

The study will use a combined microbiological and medicinal chemistry approach to advance these new anti-mastitis molecules and pave the way for  new teat care formulations.

Deosan chief executive Kip Bodle said this project provides an ideal opportunity for key stakeholders in the industry to collaborate to ensure we maintain our position as a global leader in producing quality milk.

“Our intention is to engage with government and industry leaders to ensure we are successful in commercialising products that could have global significance. Our more recent experience in the international arena strongly suggests that New Zealand innovation around milk quality resonates well with emerging dairy markets”

The Otago research team, led by Professor Greg Cook, Drs Michelle McConnell and Adam Heikal, are supported by the Auckland University team of Professor Margaret Brimble,