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Department of Medical Microbiology and Immunology

Department of Medical Microbiology and Immunology

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Departmental Mission

Our Mission is to develop new approaches for the prevention and treatment of infectious diseases and immunologic disorders. Department programs are integral to the School's new Initiative on Infectious Diseases. Researchers use state-of-the-art technologies of genomics, proteomics and imaging to study the genes and proteins of the pathogens and their hosts to identify novel targets for prevention and therapy.

 

 

New Research Findings

Breast versus bottle feeding in rhesus monkeys

 

Infants receiving different diets after birth develop distinct immune systems

 
Dr. Dennis Hartigan-O'Connor recently had a study published in Science Translational Medicine on September 3, 2014, researchers from the California National Primate Research Center (CNPRC) at UC Davis and from UC San Francisco have shown that breast-and bottle-fed infant rhesus macaques develop different immune systems. 

Diet has a strong influence on the intestinal microbiota in both humans and animal models. It is well established that microbial colonization is required for normal development of the immune system and that specific microbial constituents prompt the differentiation or expansion of certain immune cell subsets. Nonetheless, it has been unclear how profoundly diet might shape the primate immune system or how durable the influence might be. We show that breast-fed and bottle-fed infant rhesus macaques develop markedly different immune systems, which remain different 6 months after weaning when the animals begin receiving identical diets. In particular, breast-fed infants develop robust populations of memory T cells as well as T helper 17 (TH17) cells within the memory pool, whereas bottle-fed infants do not. These findings may partly explain the variation in human susceptibility to conditions with an immune basis, as well as the variable protection against certain infectious diseases.

Read more here, Published in Science Translational Medicine

Surprising discovery: HIV hides in gut, evading eradication


Lauren HiraoResearchers at UC Davis have made some surprising discoveries about the body's initial responses to HIV infection. Studying simian immunodeficiency virus (SIV), the team found that specialized cells in the intestine called Paneth cells are early responders to viral invasion and are the source of gut inflammation by producing a cytokine called interleukin-1 beta (IL-1β).

Though aimed at the presence of virus, IL-1β causes breakdown of the gut epithelium that provides a barrier to protect the body against pathogens. Importantly, this occurs prior to the wide spread viral infection and immune cell killing. But in an interesting twist, a beneficial bacterium, Lactobacillus plantarum, helps mitigate the virus-induced inflammatory response and protects gut epithelial barrier. The study was published in the journal PLoS Pathogens.

One of the biggest obstacles to complete viral eradication and immune recovery is the stable HIV reservoir in the gut. There is very little information about the early viral invasion and the establishment of the gut reservoir.

"We want to understand what enables the virus to invade the gut, cause inflammation and kill the immune cells," said Satya Dandekar, lead author of the study and chair of the Department of Medical Microbiology and Immunology at UC Davis.

"Our study has identified Paneth cells as initial virus sensors in the gut that may induce early gut inflammation, cause tissue damage and help spread the viral infection. Our findings provide potential targets and new biomarkers for intervening or blocking early spread of viral infection," she said.Satya Dandekar

In the study, the researchers detected a very small number of SIV infected cells in the gut within initial 2.5 days of viral infection; however, the inflammatory response to the virus was playing havoc with the gut lining. IL-1β was reducing the production of tight-junction proteins, which are crucial to making the intestinal barrier impermeable to pathogens. As a result, the normally cohesive barrier was breaking down.

Digging deeper, the researchers found the inflammatory response through IL-1β production was initiated in Paneth cells, which are known to protect the intestinal stem cells to replenish the epithelial lining. This is the first report of Paneth cell sensing of SIV infection and IL-1β production that links to gut epithelial damage during early viral invasion. In turn, the epithelial breakdown underscores that there's more to the immune response than immune cells.

"The epithelium is more than a physical barrier," said first author Lauren Hirao. "It's providing support to immune cells in their defense against viruses and bacteria."

The researchers found that addition of a specific probiotic strain, Lactobacillus plantarum, to the gut reversed the damage by rapidly reducing IL-1β, resolving inflammation, and accelerating repair within hours. The study points to interesting possibilities of harnessing synergistic host-microbe interactions to intervene early viral spread and gut inflammation and to mitigate intestinal complications associated with HIV infection.

"Understanding the players in the immune response will be important to develop new therapies," said Hirao. "Seeing how these events play out can help us find the most opportune moments to intervene."

Read more here, Published in Science Daily  

Diseases on the move because of climate change

Dr. ThompsonDr. George Thompson, Assistant Professor in the Department of Medical Microbiology and Immunology, was interviewed as part of a USA today article highlighting how climate change is affecting the movement of infectious diseases across the United States. Dr. Thompson is a specialist on Valley Fever, which has seen a ten-fold increase in infections since 1998.

Read more about climate change spreading diseases to new areas.

 

Surviving Valley Fever

Severe case of highlights importance of awareness, expert care

For seven months beginning in the fall of 2010, Virginia Cappel’s medical condition was touch-and-go.

The series of events that would change her life began simply, with flu-like symptoms, which Virginia and her husband Niels initially thought was bronchitis. But about a month later, when they left their home in Davis, Calif., for a vacation in the Midwest, Niels began to notice more ominous signs: disruptions in Virginia’s speech, a slower gait and confusion, such as associating the wrong words with activities.

Virginia and Niels Cappel on one of their daily walks with Woody.
Virginia and Niels Cappel on one of their daily walks with Woody.

An immediate trip to the emergency room ruled out a stroke, and during the next few weeks, the diagnosis would continue to shift. There was concern that she had bacterial meningitis, followed by viral meningitis. Finally, a neurologist diagnosed valley fever, a fungal infection that affects about 150,000 people in the U.S. each year and has been on the rise in California. According to the California Department of Public Health, the number of reported cases in California has increased six-fold, from about 816 cases in 2000 to more than 5,366 cases in 2011.

Read more about Valley Fever.