Perivascular macrophages create an intravascular niche for CD8 + T cell localisation prior to the onset of fatal experimental cerebral malaria

Qin, Jim, Michael, Lovelace D., Andrew, Mitchell J., de Koning-ward, Tania, Grau, Georges E.R., and Pai, Saparna (2021) Perivascular macrophages create an intravascular niche for CD8 + T cell localisation prior to the onset of fatal experimental cerebral malaria. Clinical and Translational Immunology, 10 (4). e1273.

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Abstract

Objectives: The immunologic events that build up to the fatal neurological stage of experimental cerebral malaria (ECM) are incompletely understood. Here, we dissect immune cell behaviour occurring in the central nervous system (CNS) when Plasmodium berghei ANKA (PbA)-infected mice show only minor clinical signs.

Methods: A 2-photon intravital microscopy (2P-IVM) brain imaging model was used to study the spatiotemporal context of early immunological events in situ during ECM.

Results: Early in the disease course, antigen-specific CD8+ T cells came in contact and arrested on the endothelium of post-capillary venules. CD8+ T cells typically adhered adjacent to, or were in the near vicinity of, perivascular macrophages (PVMs) that line post-capillary venules. Closer examination revealed that CD8+ T cells crawled along the inner vessel wall towards PVMs that lay on the abluminal side of large post-capillary venules. 'Activity hotspots' in large post-capillary venules were characterised by T-cell localisation, activated morphology and clustering of PVM, increased abutting of post-capillary venules by PVM and augmented monocyte accumulation. In the later stages of infection, when mice exhibited neurological signs, intravascular CD8+ T cells increased in number and changed their behaviour, actively crawling along the endothelium and displaying frequent, short-term interactions with the inner vessel wall at hotspots.

Conclusion: Our study suggests an active interaction between PVM and CD8+ T cells occurs across the blood-brain barrier (BBB) in early ECM, which may be the initiating event in the inflammatory cascade leading to BBB alteration and neuropathology.

Item ID: 68572
Item Type: Article (Research - C1)
ISSN: 2050-0068
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Copyright Information: This is an open access article under the terms of the Creative Commons Attribution-Non Commercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Funders: Australian Institute of Tropical Health and Medicine (AITHM), National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC APP1099920
Research Data: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026342/
Date Deposited: 21 Jul 2021 02:03
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100%
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