Origin of human innate immunity

We discovered that many components of the human cell-autonomous innate immune system evolved from defense systems that protect bacteria from phage infection (Wein, Nature Reviews in Immunology 2022). For example, we showed that the cGAS-STING antiviral pathway, originally discovered in animals, is also widespread in bacteria and protects them against phage infection (Cohen et al, Nature 2019; Millman et al, Nature Microbiology 2020). In addition, we found that genes with Toll-interleukin receptor (TIR) domains are involved in bacterial defense against phages, providing evidence for a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria (Doron et al, Science 2018; Ofir et al, Nature 2021; Leavitt et al, Nature 2022). In other studies we showed that viperins, enzymes producing antiviral molecules, evolved from bacterial enzymes that have similar functions (Bernheim et al, Nature 2021), and that a human inflammatory process called Pyroptosis also originated in bacteria (Johnson Science 2022). 

Our discoveries explain the evolution of the human cell-autonomous innate immune system. In addition to explaining how our immune system evolved, we also showed that understanding mechanisms in bacterial immune systems solves new mechanisms in the animal and plant immune systems (e.g.,  Ofir et al, Nature 2021;Leavitt et al, Nature 2022; Rousset, Cell 2023).