Remembering Pathogen Dose: Long-Term Adaptation in Innate Immunity

Recent investigations reveal memory-like adaptive responses of the innate immune system to sequential pathogen challenge. Of note, opposing effects that include both sensitization ('training') and desensitization ('tolerance') have been reported. While hitherto the nature of the pathogen was thought to be of prime importance, we propose that pathogen dose plays a key role in determining these opposing effects. Within this concept, training and tolerance of innate immune cells emerge as adaptive responses to increasing pathogen load. Furthermore, environmental stressors significantly impact the pathogen-induced responses of these innate immune cells. Therefore, we hypothesize that pathogens, like other stressors, provoke hormetic responses of the affected cells. This concept could explain the tight interplay of dose-related effects of pathogens and other stressors in infectious diseases.