Patients affected by hematological malignancies have compromised immune responses, are at higher risks of infections by a wide range of pathogens, and the resulting complications might be severe and life-threatening. Fungal infections, especially invasive aspergillosis, are an important cause of morbidity and mortality in patients with hematological malignancies undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT).
Different factors contribute to the risk of developing fungal infections. The degree of immune suppression and the exposition to environmental fungal spores clearly correlate with the risk of infection, but they provide only an incomplete picture and other risk factors likely come into play to explain why about 5-10% of patients at risk of infection actually develop the disease. Thus, it has becoming increasingly clear that the screening of patients at risk of fungal infection should include not only clinical, environmental and epidemiological considerations, but also an accurate evaluation of the immunological status of the patient. Along this line, the potential of genetic analysis to identify immunological deficits as novel risk factors is increasingly being recognized.
More recently, the study of the microbiome, i.e the entirety of microorganisms that colonize the human body, has revealed its involvement in several aspects of human physiology, ranging from nutrition to the response to stress and infections. The microbiome consists of trillions of microbial cells, representing up to 1-3% of body’s mass, that virtually colonize all externally exposed surfaces of the organism, including mouth, nose, genitals, intestine as well as the skin. Nutrients and metabolites originating from commensal bacteria work as signaling molecules with a role in development, homeostasis and activity of the immune system. Therefore, a deeper comprehension of the microbiome composition in the various districts of the human body as well as the identity of microbial metabolites is pivotal in our understanding of the immune system in the wider picture of the host-microbiome holobiont.
The results generated from this study are expected to translate in the clinical setting to estimate the individual risk of infection and identify the best strategy for both prophylaxis and antimicrobial stewardship that preserve/restore the microbial communities rather than destroying them.
The objectives of the study are as follows:
understanding of the role of the host in the microbe/fungal interaction in the lungs by evaluating the innate and adaptive immune responses.