Analyzing the role of the aging microbiota in susceptibility to Streptococcus pneumoniae

• Applicant: Dr. Christian Schulz
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Immunology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 290129999

Human life expectancy continues to increase worldwide and consequently the proportion of elderly individuals (defined as persons age 65 or older) is increasing. Germany is affected by the demographic transition in particular, having the second highest median age worldwide (44.3 years). Public spending, especially with regard to health care costs, must adapt to the health care needs of a rapidly aging demographic, as the susceptibility for diseases increases with age due to a declining immune system. Recent work from the Bowdish lab has shown that chronic age-associated inflammation impairs macrophage function. Macrophages are key players of the innate immune system and therefore the first line of defense against infectious diseases, such as community-acquired pneumonia - commonly caused by Streptococcus pneumoniae (pneumococcus). S. pneumoniae is a common, transient and generally asymptomatic member of the microbiota of the upper respiratory tract (URT) in children. In contrast, colonization of the URT in elderly occurs less frequently, but results in infection regularly. Preliminary data obtained in the Bowdish lab showed that the composition of mouse and human URT microbiota becomes dysregulated with age and inflammation. This data indicates that the changing microbiota, chronic inflammation and changing innate immune responses in the elderly synergize to increase the risk of pneumococcal infection. To test this, I will analyze how the composition of the microbiome affects susceptibility for pneumococcal infection using a unique mouse model well established in the Bowdish lab. To investigate whether young microbiota protect against S. pneumoniae infection, young (3 mos.) or old (>18 mos.) germ-free mice will be colonized with the microbiota of young or old conventionally housed SPF (specific pathogen free) mice. After infection of the mice with S. pneumoniae, I will evaluate their immune status by quantifying bacterial numbers in and leukocyte infiltration to the nasopharynx, cytokines in the blood, as well as mobilization and maturation of circulating monocytes. To subsequently elucidate the influence of the aged microbiota on the immune system in more detail, germ-free mice will be exposed to young, respectively old microbiota. By measuring cytokine levels and bacterial components in the blood, the intestinal permeability, and the macrophage function (sentinel cells of the URT), I will obtain information about how the microbiota affect immune function and inflammation. Results of this study will elucidate how synergy between the aging immune system and microbial dysbiosis contributes to pneumococcal infection and provide novel avenues of therapeutic interventions such as targeting microbial dysbiosis.

• DFG Programme: Research Fellowships
• International Connection: Canada
• Host: Professorin Dawn Bowdish, Ph.D.