Abstract
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.
Highlights
Reviewed by: Adam Denes, Institute of Experimental Medicine (MTA), Hungary Brad A
The onset of immunological alterations in the central nervous system (CNS) is sequential; neutrophils are recruited hours after stroke by activated microglia and endothelial cells, followed by monocytes a few days following the insult, whilst T and B cells infiltrate the ischaemic tissue in the succeeding weeks [28,29,30,31,32]
The interactions between microglia and monocyte-derived macrophages are indispensable for restraining and resolution of long-term microglial inflammation [61, 104] and promoting neurological recovery in diverse settings of CNS injury [95, 99]
Summary
There is a wealth of information surrounding the spectrum of immune alterations that ensue following a stroke in both patients as well as models of experimental stroke. The onset of immunological alterations in the central nervous system (CNS) is sequential; neutrophils are recruited hours after stroke by activated microglia and endothelial cells, followed by monocytes a few days following the insult, whilst T and B cells infiltrate the ischaemic tissue in the succeeding weeks [28,29,30,31,32] This contrasts immune alterations in peripheral tissues where stroke drives alterations to the hepatic cytokine networks as early as 6 h post-stroke whilst other systemic immune effects present 24 h post-stroke, affecting both myeloid and lymphoid populations [12, 14, 17, 33,34,35]. The role of non-classical monocytes following stroke is less clear in both patients and experimental models of stroke [60, 61]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
