Transregio SFB-TR 84 “Innate Immunity of the Lung: Mechanisms of Pathogen Attack and Host Defence in Pneumonia“

Pathophysiological host-pathogen crosstalk of Streptococcus pneumoniae at lung barrier interfaces (Chakraborty / Hippenstiel)

We found that pneumolysin and H₂O₂, the two major virulence factors released by Streptococcus pneumoniae (Spn), induce the endoplasmic reticulum stress sensor PERK to regulate and ameliorate maladaptive physiological changes and disrupt lung barrier function. During PERK activation, both cell autonomous- and nutritional- immunity is induced which in turn influences the production of these virulence factors.

We will examine the molecular and cellular basis of PERK-dependent induction of host stress responses and study its influence on lung barrier disruption. Our studies aim at evaluating PERK-dependent modulation as an adjuvant therapy for Spn infections in human lung tissue and animal models.