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Author summary Although invertebrates possess a comparatively simple immune system, research over the past decades revealed that a complexity of different signaling processes interact to produce fine-tuned defense responses to various pathogenic challenges. To date, however, it is still largely unexplored to what extent invertebrates generate a differentiated response against different strains of a given pathogen species. Here, we used the nematode C. elegans as a model to elucidate the common and, importantly, distinct defense responses directed at different strains of the same pathogen taxon, Bacillus thuringiensis (Bt), which vary in infection characteristics. We found that silencing of a single GATA transcriptional regulator causes protection against one Bt strain but sensitization against another. The protection is multifactorial and most likely mediated via tolerance (i.e., ability to limit cellular damage despite high pathogen burden), while sensitization results from decreased resistance (i.e., ability to limit pathogen burden through induction of antimicrobial effectors). Our work demonstrates that invertebrate defense responses against two different strains of the same pathogen species can be distinct, that they likely involve tolerance against one of the strains and are mediated by a single transcription factor as a central master switch.
