Managing cellular security systems

November 30, 2012
Microscopic image of a mouse cDC. Credit: 2012 Katsuaki Sato, RIKEN Research Center for Allergy and Immunology

Conventional dendritic cells (cDCs) are the immune system's patrol. They recognize foreign threats and trigger a defensive response, while restraining immune reactions against inappropriate targets like host proteins. They achieve the former via a mechanism called cross-presentation, which displays pieces of pathogens to cytotoxic T lymphocytes (CTLs)—the immune system's 'attack dogs'—while the latter function relies on cDC interactions with regulatory T (Treg) cells.

Katsuaki Sato's group at the RIKEN Research Center for Allergy and Immunology in Yokohama recently identified a subset of cDCs with an especially important role in fighting infection. These cells can be classified based on the proteins they show on their surface and Sato's team became especially interested in cDCs featuring a protein called CD205. "CD205+ cDCs are more efficient in the cross-presentation of cell-bound or soluble antigens to CTLs than other dendritic cell subsets," explains Sato. "However, their role in the immune system under physiological conditions was unclear."

To clarify the function of these cDCs, Sato and colleagues genetically engineered mice in which CD205+ cDCs could be quickly and selectively killed off via injection with . This depletion lasted for several days, giving the researchers a powerful way to study the specific contribution of these cells to immune function. Initial experiments with the mice provided compelling evidence that CD205+ cDCs are required to marshal an effective CTL response. Loss of these cells also resulted in abnormal Treg levels in various tissues, indicating that CD205+ cDCs are required to maintain appropriate levels of other T throughout the body.

Animals infected with high doses of the Listerium monocytogenes normally perish quickly due to septic shock resulting from immune overreaction, but CD205+ cDC-deficient animals proved resistant to and tended to survive longer, revealing a crippled inflammatory response. In the end, however, these animals were more vulnerable to bacterial infection and proliferation, resulting from impaired cDC cross-presentation of bacterial antigens to CTLs. The researchers observed similar effects with viral infection.

These results position CD205+ cDCs at a critical juncture for regulating overall immune system function as well as directed counterattacks against pathogens and the researchers see clear potential for exploiting these cells in clinical applications. "Further elucidation of CD205+ cDC function might provide insights into immune regulation and pathology and aid therapeutic interventions for infectious diseases as well as autoimmune and inflammatory disorders," says Sato. "For example, we would like to develop vaccines that selectively target CD205+ cDCs with bacterial and viral antigens."

Explore further: Study shows how immune cells rally defenses against infection while keeping harmful inflammatory reactions in check

More information: Fukaya, et al. Conditional ablation of CD205+ conventional dendritic cells impacts the regulation of T-cell immunity and homeostasis in vivo. Proceedings of the National Academy Sciences 109, 11288–11293 (2012). www.pnas.org/content/109/28/11 … df-aeca-bd12e8ea4a9a

Related Stories

Study shows how immune cells rally defenses against infection while keeping harmful inflammatory reactions in check

May 11, 2012
T cells represent a significant component of the ‘muscle’ in the immune system, promoting aggressive action against perceived threats or restraining fellow immune cells from launching an unhealthy autoimmune response ...

Skin sentry cells promote distinct immune responses

July 21, 2011
A new study reveals that just as different soldiers in the field have different jobs, subsets of a type of immune cell that polices the barriers of the body can promote unique and opposite immune responses against the same ...

How excess alcohol depresses immune function

August 16, 2011
Alcoholism suppresses the immune system, resulting in a high risk of serious, and even life-threatening infections. A new study shows that this effect stems largely from alcohol’s toxicity to immune system cells called ...

New insight into immune tolerance furthers understanding of autoimmune disease

September 15, 2011
It is no easy task to preserve the delicate balance that allows us to maintain a strong immune system that can defend us from harmful pathogens, but that is sensitive enough to correctly identify and spare our own cells. ...

Recommended for you

Study finds walnuts may promote health by changing gut bacteria

July 28, 2017
Research led by Lauri Byerley, PhD, RD, Research Associate Professor of Physiology at LSU Health New Orleans School of Medicine, has found that walnuts in the diet change the makeup of bacteria in the gut, which suggests ...

Green tea ingredient may ameliorate memory impairment, brain insulin resistance, and obesity

July 28, 2017
A study published online in The FASEB Journal, involving mice, suggests that EGCG (epigallocatechin-3-gallate), the most abundant catechin and biologically active component in green tea, could alleviate high-fat and high-fructose ...

Manipulating a type of brain cell gets weight loss results in mice

July 28, 2017
A new study has found something remarkable: the activation of a particular type of immune cell in the brain can, on its own, lead to obesity in mice. This striking result provides the strongest demonstration yet that brain ...

Team finds link between backup immune defense, mutation seen in Crohn's disease

July 27, 2017
Genes that regulate a cellular recycling system called autophagy are commonly mutated in Crohn's disease patients, though the link between biological housekeeping and inflammatory bowel disease remained a mystery. Now, researchers ...

Study finds harmful protein on acid triggers a life-threatening disease

July 27, 2017
Using an array of modern biochemical and structural biology techniques, researchers from Boston University School of Medicine (BUSM) have begun to unravel the mystery of how acidity influences a small protein called serum ...

CRISPR sheds light on rare pediatric bone marrow failure syndrome

July 27, 2017
Using the gene editing technology CRISPR, scientists have shed light on a rare, sometimes fatal syndrome that causes children to gradually lose the ability to manufacture vital blood cells.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.