RESPIRATORY VIRUSES AND IMMUNOLOGY

Respiratory infections target all ages, with infants and the elderly being most vulnerable. Young children, in particular, are very susceptible to respiratory tract infections due to their ongoing development of both the respiratory tract and immune system. Globally, respiratory syncytial virus (RSV) and influenza virus represent the most significant causes of mortality in children under the age of one year. Nonetheless, all ages are susceptible, and respiratory infections can compromise military readiness.

Because the respiratory tract is designed to maximize oxygen exchange, it is one of the most exposed mucosal surfaces; however, this interaction with the external environment leaves the respiratory tract vulnerable to toxic agents and infection from viruses and other microbes. To protect against infection, the respiratory tract is lined with immune cells that mobilize to lymphoid tissues to communicate the presence of pathogens or other molecules entering the lungs.

The intricate cellular communications that drive protection versus pathology are host-dependent, and are influenced by age, genetics, and environmental factors. To protect against respiratory pathogens, the innate immune system must take up viral antigens, process them, and present them to adaptive immune cells to effectively and specifically communicate danger.

One of the goals of our laboratory is to understand how and when immunity is initiated and communicated between the arms of the immune response, to generate protection not only against the primary infection, but also subsequent infections. Consequently, defining the fundamental communication triggers that lead to the development of memory immune cells that protect against subsequent infections is critical for vaccine design.

We focus on age-dependent changes in the ability of the host to recognize respiratory viruses and how that information is used to generate protective adaptive immunity. Dendritic cells (DC) are pivotal in recognizing pathogens and communicating this information to activate T cells and these DC exhibit unique, age-related changes in phenotype and function.

Using animal models, human cells, and in vitro human tissue models, we are exploring the mechanisms of DC activation and function in response to RSV and influenza. Our ultimate goal is to take advantage of age-dependent DC functional characteristics to more precisely design vaccines for the prevention of transmission of respiratory viral infections.

LEAD FACULTY

Allison Malloy
Annie Kilby
Mathilde Turfkruyer-Husson
Margaret Kehl