Innate immunity to bacteria: signals and mediators

The first line of defense against microorganisms is provided by the innate immune system. When pathogens break the barrier provided by the epithelia of our skin and mucosa, cells of the immune system sense infection in a process termed pattern recognition. It leads to the mobilization of an array of antimicrobial effector mechanisms, aimed at restricting further spread of the pathogen and at its eradication. The many efforts undertaken by different cell types in the course of innate immune responses must be coordinated and tightly regulated. To accomplish this task the immune system employs a large number of extracellular mediators, such as cytokines and chemokines. These polypeptides bind to cell surface receptors to stimulate intracellular signal transduction and, finally, a reprogramming of gene expression.
Listeria monocytogenes is a food-borne bacterial pathogen. It has become very popular with immunologists as a model organism for studies addressing immune responses against intracellular, nonviral infection.  Owing to its intracellular life style, L. monocytogenes is recognized by pattern recognition receptor residing in the cell cytoplasm. Signals induced by Listeria in the host cell include the IRF pathways which target type I interferon (IFN-I) genes. IFN-I are a family of cytokines that regulate immunity to both viral and nonviral pathogens. Signaling by the IFN-I receptor wires a rapid signaling track to the cell nucleus. Its simplest occurrence consists of only two components: receptor-associated Janus protein tyrosine kinases (Jaks) and transcription factors belonging to the family of signal transducers and activators of transcription (Stat). Stat target genes form large part of the antimicrobial gene expression signature of Listeria-infected cells.

Our research interests focus on the cytoplasmic recognition of L. monocytogenes, the signals causing IFN-I synthesis and the consequences of Jak-Stat signaling in infected cells and animals. To address these issues we are making intensive use of genetically modified cells and mice. Further studies investigate the consequences of viral infection on subsequent bacterial infections, seeking explanations for the frequent occurrence of bacterial superinfections in the wake of viral disease.