Patients undergoing chemotherapy for leukemia are highly vulnerable to fungal infection, and the mortality rate among patients developing invasive fungal infections is exceedingly high. Developing a better understanding of the immune defense against fungal infection, and how that is compromised in certain patients undergoing chemotherapy, could potentially lead to identifying those at risk and to development of immune-based anti-fungal therapies.
To date, scientists do not know if there are specific defects in immune resistance that mediate the susceptibility to fungal infection in this 20-25% of leukemia patients. The researchers suspect, however, that deficiencies occur in the patients' innate immune system, which ordinarily mounts a rapid but general and short-lived response. In particular, the investigators suggest that alterations occur in Toll-like receptors (TLRs), a family of cell surface receptors that play an active role in the innate resistance to microbial infection.
These TLRs ordinarily recognize molecular patterns associated with pathogens. Similar receptors are present in fruit flies and are essential to their antifungal responses. Increasing evidence suggests that mutations in human TLRs are associated with susceptibility to infections. These variations in TLRs may be associated with differences among individuals in how they respond to fungus. The researchers hypothesize that the immune system's monocytes and dendritic cells [from different individuals] will have different responses to fungus in different individuals based on genetic differences in these TLRs. They will study TLR expression, function and genetic sequence in blood cells isolated from patients prior to chemotherapy. Patient studies are essential to determine if there is an association between TLR malfunction and susceptibility to fungal infection.