Drosophila eiger Mutants Are Sensitive to Extracellular Pathogens

Abstract

We showed previously that eiger, the Drosophila tumor necrosis factor homolog, contributes to the pathology induced by infection with Salmonella typhimurium. We were curious whether eiger is always detrimental in the context of infection or if it plays a role in fighting some types of microbes. We challenged wild-type and eiger mutant flies with a collection of facultative intracellular and extracellular pathogens, including a fungus and Gram-positive and Gram-negative bacteria. The response of eiger mutants divided these microbes into two groups: eiger mutants are immunocompromised with respect to extracellular pathogens but show no change or reduced sensitivity to facultative intracellular pathogens. Hence, eiger helps fight infections but also can cause pathology. We propose that eiger activates the cellular immune response of the fly to aid clearance of extracellular pathogens. Intracellular pathogens, which can already defeat professional phagocytes, are unaffected by eiger. We show that the gene eiger, which is the sole tumor necrosis factor homolog in the fruit fly, can play opposing roles in the fly's response to infections. Sometimes eiger contributes to the disease induced by an infection, while at other times it is required to fight an infection. Commonly, the fly's immune response is described as dividing microbes into two groups with Gram-positive bacteria and fungi lying in one group and Gram-negative bacteria lying in the other. Pathogenic bacteria can also be divided into two groups based on their behavior in eiger mutant flies, but these two groups differ from past descriptions. eiger tends to be required for the innate immune response against extracellular pathogens but tends to cause pathology during an infection with an intracellular pathogen. We suggest that eiger is required for innate immune responses that are effective at fighting extracellular pathogens but are wasteful or simply ineffective when fighting intracellular pathogens. We show here that the fly immune response is more complex than previously recognized and suggest new directions for studying pathogenesis in addition to innate immunity in the fly.