Respiratory infections, including pneumonia, tuberculosis and influenza, are collectively the leading causes of death worldwide. The immune system’s role in protecting the lungs against the constant threat from inhaled pollutants and aspirated pathogens is particularly challenging, as it must be accomplished without compromising gas-exchange by excessive inflammation. Lymphocytes are essential components of protective adaptive immunity, but also orchestrate organ damage in tissue-specific inflammation. By studying the mechanisms that regulate lymphocyte number and function in murine models of lung inflammation, we seek novel insights to prevent and treat respiratory infections and chronic lung diseases such as asthma, COPD and sarcoidosis.
The Curtis lab itself has published extensively on the response induced by intratracheal challenge of primed mice with the particulate antigen sheep red blood cells (SRBC). This particulate, non-replicating CD4-dpependent antigen induces intense, self-limiting lung inflammation. We have used the response to characterize the contribution of death by apoptosis and local proliferation to the maintenance of lung lymphocyte numbers, and to analyze the roles of endothelial selectins and lung chemokines in recruitment of various leukocyte subsets to the lungs.
We also continue to examine these experimental questions in collaboration with other laboratories, employing murine models of lung infection with Cryptococcus neoformans, Pneumocystis murina, Vaccinia & Rhinoviruses and Haemophilus influenzae.
These studies use wild-type and gene-targeted mice, and a variety of techniques, notably multi-color flow cytometric analysis on our LSR II instrument, to investigate the molecular basis for maintenance of leukocyte numbers within the lungs. These studies are funded by R01 HL056309 from NHLBI, and by the Biomedical & Laboratory Research Service, Department of Veterans Affairs.