In late 2000, after finishing my PhD and starting an overseas postdoctoral position, I was ready to move on from the topic of stroke. I was eagerly examining how immune cells in the liver are crucial for host antibacterial defence. However, I came across a paper that provided the first experimental proof of brain-mediated peripheral immune impairment in stroke, and I was back in the field of stroke once again.

Stroke-induced systemic immunosuppression and the subsequent development of infection were first described in the 1970s. These early observations challenged the accepted idea that fatal bacterial pneumonia following stroke arises simply due to aspiration secondary to dysphagia (difficulty swallowing). In 2003, Prass et al. provided a mechanistic basis for these observations and elegantly demonstrated that catecholamine-mediated lymphocyte dysfunction was the key factor in the impaired antibacterial immune response after stroke. Their study revealed that impaired natural killer cell and T cell function, particularly in their ability to produce IFNγ, is the crucial stroke-induced deficit in host antibacterial defence. Adoptive transfer of IFNγ-producing lymphocytes or early treatment with recombinant IFNγ was effective in halting bacteraemia and pneumonia after stroke, with both strategies clearly restoring immunity independent of aspiration.

the injured post-stroke brain transmits signals of immunosuppression via stress pathways

It turns out that the injured post-stroke brain transmits signals of immunosuppression via stress pathways, namely the sympathetic arm of the autonomic nervous system. Inhibitors of the sympathetic adrenergic receptors efficiently limit lymphocyte dysfunction and bacterial infections after stroke. This discovery triggered subsequent efforts to reveal novel mechanisms and potentially harness neuroendocrine pathways to improve stroke outcomes. In addition, this study has broad implications in the field of immunology. Physiological systems have long been studied in isolation from each other. This study highlighted that immune cells are not only self-regulated but also function in close association with many other cell types, such as neurons, to maintain homeostasis and provide effective host responses to injury.