A large number of pathogenic microbes must be recognized by the immune system and defense mechanisms must be alerted. The first line of defense is set by the innate immune system which rapidly limits antimicrobial and colonization and spread. To increase protection cells participating in the innate response initiate an adaptive immune response. Protection and immunoregulation by the innate immune system requires that a microbe is detected and physical contact is translated into altered gene expression of the infected cell.

Antimicrobial gene products provide protective effector mechanisms. Moreover, secreted cytokines fulfill the task of communicating between cells involved in the antimicrobial response to maximize the common antimicrobial effort. One important group of cytokines is formed by the interferons (IFN), subdivided into three distinct classes (IFN-I, II, III). Collectively IFN play an indispensable role in the immune system as humans or animals with partial or complete losses of responses to IFN are highly immunecompromised. To reprogram gene expression in target cells, IFN employ Jak-Stat signal transduction: after binding to cell surface receptors, receptor- associated Jak tyrosine kinases phosphorylate Stat transcription factors which translocate to the nucleus to stimulate gene expression. 

Our research aims at understanding how the synthesis of IFN-I is regulated when cells or animals are infected with intracellular bacteria and how the Stats activated upon IFN-I secretion communicate with additional bacteria-derived signals in the process of activating antimicrobial genes.  To this end we infect normal cells and mice and compare them with infected mice that cannot synthesize IFN-I or that cannot respond to them. In addition, mice with reduced or absent responses to IFN are used to study the impact of the cytokines in a mouse model of acute intestinal inflammation. In this situation we test the hypothesis that IFN contribute to inflammation, thus worsening the outcome. These efforts are coordinated with collaborators at the University of Vienna that determine corresponding changes in the composition of the intestinal microbiota.

Infections to viral pathogens such as influenza virus are frequently followed by superinfection with a bacterial pathogen and severe disease may result from the bacterial rather than the original viral infection.  In her project, Amanda Jamieson studies mechanisms causing the immune response to influenza virus to alter and worsen the subsequent infection by a bacterial pathogen. Her recent work points towards an important role of influenza-induced glucocorticoids in suppressing the immune response to a superinfecting bacterial pathogen.