Career Development Projects

CD003 Purdy

Old age is associated with a decline in immunity and increased susceptibility to infectious disease. The elderly would be particularly susceptible to respiratory pathogens that are select agents. In the 2001 inhalation anthrax attacks, the median age of individuals sickened was 56 years. The increased incidence of infection suggests there are defects in the initial innate immune response, including the ability of the innate immune system to detect microbes and respond effectively. Macrophages are multifunctional cells that are key players in innate immunity. Alveolar macrophages are the target cells for the select agents MDR/XDR-TB, Francisella tularensis, and Burkholderia pseudomallei.  To further understand the role of aging on innate immune control of human respiratory pathogens, we are developing a non-human primate alveolar macrophage model. In this project we will functionally characterize alveolar macrophages from young and old macaques in order to answer the following questions:

1. How does aging affect the innate immune functions of alveolar macrophages and does it contribute to increased susceptibility to respiratory pathogens? The ability of alveolar macrophages from young and old animals to phagocytose material and deliver it to the hydrolytic lysosome will be compared. The response by alveolar macrophages from young and old macaques to pathogen-associated molecular patterns (PAMPS) and intact bacteria will be defined. 

2. Does the reduction of autophagy in aged immune cells contribute to the age-related decline in immunity and increased susceptibility to infection? Data indicates that the efficiency of autophagy in aged cells is reduced.  Levels of autophagy in resting and autophagic alveolar macrophages will be quantified and the ability of autophagic macrophages to clear respiratory pathogens will be defined.