Allergic Reactions Offer Protection Against Yeast-Triggered Asthma, Research Finds

We think about asthma and others allergic diseases such as unnecessary aberrant immune responses that do more harm than good. However, new evidence from an international team led by researchers at Baylor College of Medicine shows that certain allergic reactions provide needed protection against highly invasive and potentially fatal infectious agents, such as yeast.

Working with an animal model of yeast-triggered asthma commonly seen in humans, researchers discovered a molecular mechanism by which yeast activates platelets to mediate an allergic immune response that clears yeast from the lungs. In the absence of platelets, the yeast can overgrow and lead to a rapid and fatal outcome. As reported in the journal Immunity, this work is one of the first to show a clear molecular pathway supporting the role of platelets in the immune response.

“A common yeast called Candida albicans is a well-known cause of allergic diseases of the human respiratory tract, such as asthma, ”said corresponding author Dr David B. Corry, professor of medicine-immunology, allergy and rheumatology and holder of the Fulbright Chair in Pathology at Baylor. “However, the mechanisms by which yeast triggers asthmatic reactions are poorly understood. “

In addition to yeast, mold is also a major cause of human allergies. Corry and his colleagues had previously shown that mold triggers an allergic immune response by producing a type of enzyme called protease. The enzymes activate T helper type 2 (Th2) and T helper type 17 (Th17) immune cells, which mediate the allergic response.

Mold and yeast are two types of fungi. “Candidiasis also makes proteases, so we hypothesized that its proteases, like those in mold, would also be involved in promoting an allergic immune response, ”said Corry, member of the Dan L Duncan Comprehensive Cancer Center at Baylor . “We actually found something completely different. “

A new role for candidalysin

Working with a mouse model of yeast-triggered asthma, we found that Candidiasis proteases do not drive allergic immune responses mediated by Th2 and Th17. Instead of, Candidiasis promotes these types of immune responses by producing the peptide candidalysin. “

Dr Yifan Wu, co-first author of the study, postdoctoral associate, Corry laboratory

Peptides, like proteins, are made up of amino acids linked together like beads on a necklace, but contain fewer amino acids than proteins. Candidalysin was originally described as a peptide toxin unique to Candidiasis, able to lyse or disintegrate cells. In this study, Corry, Wu and their colleagues discovered that candidalysin can also trigger an allergic immune response and the mechanism that mediates it.

Researchers have found that candidalysin binds to the GP1b-alpha receptor, a molecule on the surface of platelets. This binding prompted the platelets to release a protein called Dkk-1, which in turn resulted in Th2 and Th17 allergic responses that correlate with reduced lung yeast loads in experimental animal models.

“Our results show that when animal models produce an asthmatic response, they eliminate Candidiasis in the lungs very efficiently, “Wu said.” On the other hand, in the absence of platelets, there is no allergic response and Candidiasis spreads unchecked, resulting in rapid death. “

Support the role of platelets in the immune response

Platelets are well known for their role in mediating blood clotting to stop or prevent bleeding. In this study, Corry, Wu and their colleagues are the first to provide molecular evidence for another role for platelets as active contributors to the immune response.

When Candidiasis enters the respiratory tract, the authors explain, platelets react in two ways to fight infection. On the one hand there is a Candidiasis infection that very quickly becomes invasive when the yeast burrows into the lung tissue, ruptures and enters the blood vessels where it can migrate to other places in the body. In response to this invasion, platelets activate their blood clotting function to reduce Candidiasisadvances.

“Regardless of their clotting function, we have found that platelets respond to candidalysin by promoting the development of allergic immune responses mediated by Th2 and Th17 which confer immunological protection against Candidiasis“Wu said.” This molecular pathway supports the role of platelets in the immune response. “

“We are very excited to crystallize the idea that platelets are essential immune cells and the possibility of their roles in other conditions,” said Corry.