Neuroimmunology studies communication between the nervous and the immune systems ? arguably among the most complicated systems of our body. We have demonstrated that the two systems are closely integrated unlike what was previously assumed and have identified the meninges as the place through which immune cells mediate their effect. We have also (re)discovered meningeal lymphatic vessels and demonstrated that these vessels serve as a communication route between the brain and immunity. The brain is our computing machine that integrates stimuli from the environment and orchestrates responses to these stimuli. But we have evolved and live in the world of microorganisms. It is unconceivable to imagine that the brain would give up on ?sensing? the microorganisms. In this proposal, we will test the hypothesis that the defining role of the immune system is to sense microorganisms and inform the brain about them. We propose that the immune responses are hardwired within our brain with connections to numerous circuits. These connections create a ?neuroimmune connectome?, altering which interferes with brain function. We will concentrate our efforts to decipher the neuroimmune connectome, to unravel the mechanism through which immune cells inform the brain of commensals and pathogens, and understand the consequences of brain?s response to immunological ?information?. Understanding immune inputs into brain circuitry could be the key to understanding neurological manifestations of diseases impacted by the immune system as well as the mechanisms of actions underlying the impacts of conventional and complementary/integrative therapies on diseases.