How do white blood cells detect invaders to destroy?

Scientists at Cedars-Sinai Medical Center have discovered how a molecular receptor on the surface of white blood cells identifies when invading fungi have established direct contact with the cell surface and pose an infectious threat.

The receptor called Dectin-1, studied in the laboratory of David Underhill, PhD, an associate professor in Cedars-Sinai's Inflammatory Bowel and Immunobiology Research Institute, detects fungi and instructs whether to expend the energy needed to devour the invading pathogens. The findings are featured as the cover story in the April 28 edition of Nature.

Although scientists long have theorized how immune cells recognize microbial debris sloughed from invading organisms at some distance from themselves, this study establishes a model to explain how immune cells determine when pathogens are directly in contact with their surface and thus pose a significantly greater risk, demanding rapid destruction.

The study is important because it moves scientists one step closer to understanding the mysteries of how our bodies mount an immune response to fight disease.

In early stages of infection, white blood cells patrol the body looking for invading pathogens. Dectin-1, a receptor on the surface of white blood cells, recognizes specific components of fungal cell walls, and alerts or "switches on" the to prepare to fight the infection.

"Our lab has been studying Dectin-1, which directs white blood cells to eat and kill the fungi that they encounter directly, but to ignore soluble material sloughed off of the fungal surface which does not pose an immediate threat," said Helen Goodridge, PhD, first author on the study and a researcher in the laboratory headed by Underhill. "This is important because phagocytosis and anti-microbial defense responses are energy-intensive and destructive, and should only be used when absolutely necessary."

During phagocytosis, a white blood cell encounters a microbe, engulfs it, and eats it. Once inside the cell, the microbe can be killed using a combination of degradative enzymes, highly reactive chemicals, and an acidic environment.

A molecular structure that the Underhill lab calls a "phagocytic synapse" forms at the surface of the white blood cell when Dectin-1 detects . As a phagocytic synapse forms, two inhibitory proteins that block transmission of signals inside the white blood cell are pushed aside. This allows Dectin-1 to instruct the cell to respond. The phagocytic synapse does not form when Dectin-1 encounters soluble fungal debris, so the white blood cell does not respond.

"The phagocytic synapse resembles another molecular structure, the 'immunological synapse.' It is critical at later stages of an immune response," said Underhill. "It appears that the phagocytic synapse may be an evolutionary precursor of the immunological synapse."

Provided by Cedars-Sinai Medical Center

1 /5 (1 vote)

Related Stories

White blood cells are picky about sugar

Jul 11, 2007

Biology textbooks are blunt—neutrophils are mindless killers. These white blood cells patrol the body and guard against infection by bacteria and fungi, identifying and destroying any invaders that cross ...

Mounting a multi-layered attack on fungal infections

Sep 08, 2009

Unravelling a microbe's multilayer defence mechanisms could lead to effective new treatments for potentially lethal fungal infections in cancer patients and others whose natural immunity is weakened.

Vitamin A signals offer clues to treating autoimmunity

Mar 01, 2009

Distributed around the body, dendritic cells act as the security alarms of the immune system. After sensing the presence of intruders, dendritic cells can transmit the alarm to white blood cells or tell them to relax, depending ...

Researchers study benefits of white button mushrooms

Jul 29, 2010

Mushrooms are among the many foods thought to play an important role in keeping the immune system healthy. Now, Agricultural Research Service (ARS)-funded scientists have conducted an animal-model and cell-culture study showing ...

Images shed new light on inflammation (w/ Video)

Oct 15, 2010

Researchers at the University of Calgary Faculty of Medicine are using an innovative new imaging technique to study how white blood cells (called neutrophils) respond to inflammation, and have revealed new targets to inhibit ...

Recommended for you

Small RNAs in blood may reveal heart injury

4 hours ago

(Medical Xpress)—Like clues to a crime, specific molecules in the body can hint at exposure to toxins, infectious agents or even trauma, and so help doctors determine whether and how to treat a patient. ...

Researchers uncover clues to flu's mechanisms

9 hours ago

A flu virus acts like a Trojan horse as it attacks and infects host cells. Scientists at Rice University and Baylor College of Medicine have acquired a clearer view of the well-hidden mechanism involved.

User comments