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Melbourne researchers have made a breakthrough in the understanding of immunity against the globally important human pathogen, Salmonella enterica.  

Salmonella enterica includes bacteria that cause local gut disease like gastroenteritis, as well as severe, life threating invasive diseases like typhoid fever. 

Working on a model of typhoid fever the team - led by Melbourne University Professor Sammy Bedoui and Melboune University Professor Dick Strugnell from the Peter Doherty Institute for Infection and Immunity (the Doherty Institute) developed a method for studying the development of immunological memory.

In a paper recently published in PLOS  University of Melbourne PhD graduate, Dr Newton Peres, in collaboration with research fellow Dr Nancy Wang, also from the University of Melbourne’s Department of Microbiology and Immunology, showed that immunity in Salmonella infections started in the central lymphoid organs and developed further in the peripheral tissues, like the liver.

In early experiments published in PNAS (Proceedings of the National Academy of Sciences) in 2018, the researchers demonstrated that the liver held immune 'memory' for the bacterial pathogen, mediated by a type of T cells that operate locally within the liver. 

“To study these tissue-associated cells outside the host, it was necessary to protect them against themselves,” Dr Peres said.  “These tissue-associated helper T cells have a capacity to 'self-destruct' once removed from the tissue, making analysis much more difficult.” 

Dr Peres and the research team showed that if this self-destruct process was blocked, it was possible to isolate and study the immune cells in the liver.

“Our observations highlight the importance of triggering immunity against systemic infections in the liver” he said. “This was quite interesting given that much of the previous work around immunity against Salmonella infection has focussed on T cells in the blood and lymphoid organs”.

In the recent PLoS pathogens study, Dr Peres and Dr Wang showed that there was a brief period early in the infection, when the immune cells are present in the circulation, and that these circulating cells, which are CD4+ T cells, can be given to a non-immune animal to provide protection against challenges with Salmonella.   

“It is recognised that loss of CD4+ T cells, which happens during HIV infection, makes humans much more sensitive to Salmonella infections,” Dr Peres said.

“Now that we know more where the cells that mediated protection against Salmonella infection reside, this work will create momentum for ongoing studies to identify the key elements of the bacteria that are recognised by the immune system of protected animals.  Identifying these antigens will be key to the possible development a new Salmonella vaccine based on the purified constituents.”

Professor Bedoui’s research at the Doherty Institute has defined how particular types of T cells protect the host from Salmonella infections and has shed new light into understanding how dendritic cells integrate multiple signals into protective immunity against many infections, including Salmonella.

Professor Strugnell’s research involves two key human pathogens, Salmonella enterica and Klebsiella pneumoniae.  The bacteria include organisms responsible for severe human diseases in developed and less-developed healthcare settings.  The research leads to new interventions which include antimicrobials targeting key physiological processes e.g. growth, inhibitors of bacterial adhesion and novel strategies to exploit our growing understanding of the microbe/immune system interface such as immunomodulatory drugs and biologicals and new or improved vaccines to prevent disease.

The studies were conducted in collaboration with Professor Stephen McSorley, University of California and collaborators from The University of Bonn, James Cook University, and the University of Adelaide.