Meningitis occurs when bacteria enter the lining of the brain and trigger an inflammatory response. In Nature, Pinho-Riberio et al. find that during meningitis, bacteria can stimulate nociceptors in the meninges to release calcitonin gene-related peptide (CGRP), which suppresses macrophage activity and exacerbates disease. Mice were intravenously injected with Streptococcus pneumoniae or Streptococcus agalactiae to induce bacterial meningitis. Depletion of nociceptors resulted in decreased bacterial loads in the meninges and brain, and increased immune cell infiltrate in the meninges. Bacterial pathogens activated nociceptors, resulting in the release of CGRP. CGRP signals through receptor activity modifying protein 1 (RAMP1), which is expressed by meningeal macrophages. When RAMP1 expression was ablated in macrophages, there were decreased bacterial loads in the meninges and brain, increased macrophage expression of Cxcl10, Ccl3, Ccl2 and Tnf, and increased numbers of neutrophils and monocytes in the meninges. Thus, bacterial invasion results in CGRP release, which suppresses the activity of meningeal macrophages and enhances bacterial invasion.