Old Dog New Tricks; Revisiting How Stroke Modulates the Systemic Immune Landscape

• Main Authors: Siddharth Krishnan, Catherine B. Lawrence
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-07-01
• Series: Frontiers in Neurology
• Subjects: cerebral ischaemia; post-stroke infection; systemic immunity; innate immune training; neuroimmunology
• Online Access: https://www.frontiersin.org/article/10.3389/fneur.2019.00718/full

Infections in the post-acute phase of cerebral ischaemia impede optimal recovery by exacerbating morbidity and mortality. Our review aims to reconcile the increased infection susceptibility of patients post-stroke by consolidating our understanding of compartmentalised alterations to systemic immunity. Mounting evidence has catalogued alterations to numerous immune cell populations but an understanding of the mechanisms of long-range communication between the immune system, nervous system and other organs beyond the involvement of autonomic signalling is lacking. By taking our cues from established and emerging concepts of neuro-immune interactions, immune-mediated inter-organ cross-talk, innate immune training and the role of microbiota-derived signals in central nervous system (CNS) function we will explore mechanisms of how cerebral ischaemia could shape systemic immune function. In this context, we will also discuss a key question: how are immune requirements critical for mediating repair of the ischaemic insult balanced by the need for anti-microbial immunity post-stroke, given that they are mediated by mutually exclusive immune networks? Our reformed understanding of the immune landscape post-stroke and novel mechanisms at play could guide targeted therapeutic interventions and initiate a step-change in the clinical management of these infectious complications post-stroke.