This Progress article describes recent studies showing that the human lipopolysaccharide sensor caspase-4 activates pro-IL-18 and causes vascular leakage by inducing pyroptosis in endothelial cells. Structural studies have uncovered allosteric sites of caspase-4 that might be effective drug targets to inhibit vascular leakage.

HIV infection persists under antiretroviral therapy due to a reservoir of latently infected cells. This Perspective discusses how host immune responses might affect the establishment and persistence of the viral reservoir, an understanding of which supports the development of immune-based approaches to ‘cure’ HIV infection by disrupting the reservoir.

B cells are major drivers of systemic immunity, but they also act locally in non-lymphoid organs. This Review highlights new insights into mechanisms of tissue B cell function as well as efforts to leverage this biology for immunotherapy.

The peripheral immune system communicates with the brain through diverse anatomical routes to shape brain physiology. Here we discuss why such diversity is needed and explore how these routes are leveraged during development and hijacked in ageing.