{"id":142263,"date":"2018-11-07T08:03:36","date_gmt":"2018-11-07T13:03:36","guid":{"rendered":"https:\/\/today.uconn.edu\/?p=142263"},"modified":"2018-11-07T08:15:37","modified_gmt":"2018-11-07T13:15:37","slug":"t-cells-stay-put-key-better-salmonella-vaccine","status":"publish","type":"post","link":"https:\/\/today.uconn.edu\/2018\/11\/t-cells-stay-put-key-better-salmonella-vaccine\/","title":{"rendered":"T Cells That Stay Put Could Be Key to a Better Salmonella Vaccine"},"content":{"rendered":"

University of Connecticut and University of California-Davis researchers announced in the Proceedings of the National Academy of Sciences on Sept. 25<\/a> a breakthrough in understanding which cells protect against\u00a0Salmonella<\/a>\u00a0<\/em>infection \u2013 a critical step in developing a more effective and safe vaccine against a bacterium that annually kills an estimated one million people worldwide.<\/p>\n

Salmonella typhi\u00a0<\/em>causes life-threatening enteric fever (historically called typhoid fever), commonly in Africa and parts of Asia. Other strains of\u00a0Salmonella\u00a0<\/em>are capable of causing gastroenteritis or invasive non-typhoidal Salmonellosis (NTS), an emerging disease in sub-Saharan Africa. Enteric fever and NTS can be fatal in 20 to 25 percent of infected individuals without access to medical care.<\/p>\n

There are two vaccines currently available for\u00a0Salmonella<\/em>, but neither are practical for use in sub-Saharan Africa and they only protect about 50 percent of people immunized.<\/p>\n

\n

What hasn\u2019t been realized until very recently is there are actually two different categories of T cells \u2013 those that circulate through tissues in the body and those that never move. — Stephen McSorley<\/cite><\/p>\n<\/blockquote>\n

A collaborative group of scientists from the University of Melbourne, Australia, UConn Health, and the University of California-Davis decided to investigate how the vaccines work, in order to understand how they could be improved. They focused on a relatively unknown type of immune cell, called non-circulating memory T cells. Memory T cells are long-lived and are the immune system’s recall mechanism. When they re-encounter a bacteria, virus, or other pathogen they’ve seen before, they quickly multiply and alert the rest of the immune system to the invasion.<\/p>\n

\u201cWhat everyone has been focused on in immunology\u00a0\u2013 not just in addressing\u00a0Salmonella<\/em>, but all infectious diseases for the past 50 years or so\u00a0\u2013 has been antibody and T cell responses,\u201d said Stephen McSorley, lead author and interim director of the Center for Comparative Medicine at UC Davis. \u201cWhat hasn\u2019t been realized until very recently is there are actually two different categories of T cells \u2013 those that circulate through tissues in the body and those that never move and are known as tissue-resident or non-circulating memory cells.\u201d<\/p>\n

Since non-circulating memory T cells were discovered, McSorley said, there\u2019s been a rush in different disease models to understand whether they are important or not \u2013 in cancer and infectious diseases. It seems in some models they are very important; in others, they are less so.<\/p>\n

During the study, graduate students from UC Davis made several trips to UConn to conduct experiments in collaboration with UConn immunologist Lynn Puddington and her team, experts in the definitive approach to distinguish circulating versus resident cells. The technique involves connecting and then disconnecting the circulatory systems of unrelated mice. One mouse in each pair had been vaccinated against Salmonella;<\/em> the other mouse had not.\u00a0Thanks to fluorescent markers, the team was able to show that the T cells that protected against\u00a0Salmonella\u00a0<\/em>infection lived in the vaccinated mouse’s liver, and stayed there. They never made it to the unvaccinated mouse’s liver. These cells were obviously non-circulating T cells.<\/p>\n

\u201cThis evidence that non-circulating T cells play a key role in protection from this major pathogen is really exciting,\u201d says Puddington. Generating these cells may be the basis of future vaccines against typhoid and NTS.<\/p>\n

Current Salmonella vaccines limited<\/strong><\/p>\n

Non-typhoidal Salmonellosis has really emerged in Africa in the past 10 years, mainly in young children, the elderly, and HIV positive individuals \u2013 basically, people with compromised immune systems. They get a strain that would normally cause stomach upset, but in these individuals, it causes systemic infection and can kill them.<\/p>\n

\u201cThe goal of our lab is to understand the mechanisms of protective immunity in mice to learn tricks of the immune system, and then develop a vaccine that could replicate that to use for kids and people who live in these areas,\u201d UC Davis’s McSorley said. \u201cWe found that you absolutely need these non-circulating T cells to protect against\u00a0Salmonella<\/em>. That\u2019s an important milestone, because if you\u2019re going to make a vaccine, you have to know what you\u2019re trying to induce with that vaccine. Now that we know these forms of T cells exist and protect against\u00a0Salmonella<\/em>, the next goal is to try to develop synthetic ways to induce them to make a vaccine.\u201d<\/p>\n

McSorley said they have some ideas about how to do that, and that\u2019s where the next phase of their research is going \u2013 to try and take vaccine components in a mouse model to focus specifically on these non-circulating cells and see if they can induce them.<\/p>\n

\u201cIf we can learn how to better induce them and if we can apply that to a new\u00a0Salmonella\u00a0<\/em>vaccine,” he said, “it should be more efficient at providing immunity than previous vaccines.\u201d<\/p>\n

Co-authors include Joseph Benoun, Oanh Pham, Victoria Rudisill, and Zachary Fogassy from UC Davis\u2019s School of Veterinary Medicine; Newton Peres, Nancy Wang, Paul Whitney, Daniel Fernandez-Ruiz, Thomas Gebhardt, Sammy Bedoui, and Richard Strugnell from the University of Melbourne; and Quynh-Mai Pham and Lynn Puddington from UConn Health.<\/p>\n

This study was supported by grants from the NIH\u2019s National Institute of Allergy and Infectious Diseases and the National Health and Medical Research Council of Australia.<\/em><\/p>\n

Trina Wood is a communications officer for the UC\u00a0Davis School of Veterinary Medicine. Twitter:\u00a0@ucdavisvetmed<\/a><\/em><\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

UConn and UC Davis researchers announced a breakthrough in understanding which cells protect against\u00a0Salmonella\u00a0\u2013 a critical step in developing a better vaccine against the often deadly bacterium.<\/p>\n","protected":false},"author":79,"featured_media":142592,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"wds_primary_category":0,"wds_primary_series":0,"wds_primary_attribution":0,"footnotes":""},"categories":[2231,2076,179],"tags":[],"magazine-issues":[],"coauthors":[1899],"class_list":["post-142263","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health-well-being","category-research","category-uconn-health"],"pp_statuses_selecting_workflow":false,"pp_workflow_action":"current","pp_status_selection":"publish","acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-07-23 18:54:52","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/142263","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/users\/79"}],"replies":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/comments?post=142263"}],"version-history":[{"count":9,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/142263\/revisions"}],"predecessor-version":[{"id":143519,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/142263\/revisions\/143519"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media\/142592"}],"wp:attachment":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media?parent=142263"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/categories?post=142263"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/tags?post=142263"},{"taxonomy":"magazine-issue","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/magazine-issues?post=142263"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/coauthors?post=142263"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}