Immunological insights into Epidermal Growth Factor Receptor Signaling Implications for host pathogen interactions

Abstract

Infectious diseases account for a large proportion of morbidity and mortality worldwide. The major global efforts lie in effectively enhancing the health span of infected individuals and more importantly, curbing infection onset and spread. A multitude of host- and pathogen-derived factors contribute towards coining the outcome of infections. In this regard, the virulence of major successful infectious agents is believed to be determined by their prowess to swivel host immune system to their own benefit. The pathogens effectuate such immune subversions by modulating various host signalling pathways and reprogramming host cellular homeostatic processes. Thus, understanding the transactions occurring at the host-pathogen interface becomes an asset for the development of rational diagnostic, preventative and therapeutic interventions for infectious diseases. The current study focuses on the implications of Epidermal Growth Factor Receptor (EGFR) signalling during selected bacterial infections. Conventionally associated with cancers of various origins; accumulating evidences indicate aberrant activation of EGFR (Receptor Tyrosine Kinase, RTK) pathway during infection scenarios and Pattern Recognition Receptor (PRR) engagements. For instance, EGFR has been reported to be deregulated during infections with Helicobacter pylori, Shigella flexneri, Mycobacterium tuberculosis and Toxoplasma sp.; however, there is a dearth of information relating to the molecular mechanisms governed by EGFR during such infections. In the purview of the stated literature, the specific contributions of EGFR in the pathogenesis of Mycobacterium tuberculosis (Mtb) and Shigella flexneri (S. flexneri) was conceived. Infection with both Mtb and S. flexneri activated signalling through EGFR pathway. During Mtb infection, EGFR was intricately involved in regulating key processes that allow pathogen survival. EGFR was found to employ a specific reader of epigenetic marks, Bromodomain-containing protein 4 (BRD4), to alter gene expression and assist...