Balachandran Ravindran
The current conundrum of inflammation is that exogenous pathogen-associated molecular patterns (PAMPs) from microbial sources or endogenous damage-associated molecular patterns (DAMPs) released during trauma/tissue injury generate host inflammatory response independently or in a synergistic manner. The 'discussion' highlights several confounders in the in vitro investigations reported in the literature and argues in favour of addressing the issue only in in vivo model systems, such as germ-free animals that are free of microbiota and hence PAMPs, in which response to DAMPs can be precisely studied. Based on the available literature, the 'discussion forum' proposes that host innate immune responses leading to the induction of inflammatory molecules by PAMPs and DAMPs are interdependent and biologically inactive in isolation, and that their threshold and context would be critical determining factors for acute or chronic inflammation.