Overview
Infections in the lower airway are the leading cause of death in the first year after a lung transplant. The drugs that stop the body rejecting a new lung work by dampening the immune system, which leaves recipients less able to fight off organisms that a healthy person would clear without noticing.
What makes this difficult is that infections behave unpredictably. The same bacterium can be cleared quietly in one recipient and set off an immune reaction in another that damages the new lung. Sometimes the organism itself causes little harm and the body's response causes most of the damage.
Our research treats infection and rejection as connected rather than separate problems. The practical question is how to tell a helpful immune response, one that is clearing an infection, from a harmful one that is injuring the transplant, because those two situations call for opposite treatments.
Fungal recognition and Dectin-1
We identified deficiency in Dectin-1 as a risk factor for chronic lung allograft dysfunction and death. Dectin-1 is an immune sensor that recognizes beta-glucans, a building block of the cell walls of fungi including Aspergillus, and it is carried by several cell types in the airway. People differ in how well this sensor works, and those differences appear to matter for transplant outcomes. Later work examined how weakened recognition through this pathway changes the airway's response to fungal exposure.
Pseudomonas in cystic fibrosis recipients
In recipients whose original disease was cystic fibrosis, we found that the cells lining the airway showed suppressed interferon responses during Pseudomonas infection. Interferons are signaling proteins that are central to defense against viruses and bacteria, and a blunted response in this setting may help explain why Pseudomonas behaves differently in these patients than in other recipients.
Cytomegalovirus
Cytomegalovirus is a common virus that most people carry harmlessly for life but which can reactivate when the immune system is suppressed. We developed a score based on chemical marks on DNA that predicts which previously exposed recipients are likely to develop detectable virus in the blood. We also identified a population of immune cells associated with prior cytomegalovirus exposure that was linked to viral control in kidney transplantation and to chronic graft dysfunction in lung transplantation.
Faster diagnosis and the airway microbiome
We have worked on identifying airway pathogens by detecting their genetic material directly, which is faster than growing the organism in culture and can shorten the time before the right treatment starts. We also study the community of microbes living in the transplanted airway and the antibiotic resistance genes it carries.