Olfactory plays a key role in spatiotemporal pathogenesis of cerebral malaria.

Abstract:

:Cerebral malaria is a complication of Plasmodium falciparum infection characterized by sudden coma, death, or neurodisability. Studies using a mouse model of experimental cerebral malaria (ECM) have indicated that blood-brain barrier disruption and CD8 T cell recruitment contribute to disease, but the spatiotemporal mechanisms are poorly understood. We show by ultra-high-field MRI and multiphoton microscopy that the olfactory bulb is physically and functionally damaged (loss of smell) by Plasmodium parasites during ECM. The trabecular small capillaries comprising the olfactory bulb show parasite accumulation and cell occlusion followed by microbleeding, events associated with high fever and cytokine storm. Specifically, the olfactory upregulates chemokine CCL21, and loss or functional blockade of its receptors CCR7 and CXCR3 results in decreased CD8 T cell activation and recruitment, respectively, as well as prolonged survival. Thus, early detection of olfaction loss and blockade of pathological cell recruitment may offer potential therapeutic strategies for ECM.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

Zhao H,Aoshi T,Kawai S,Mori Y,Konishi A,Ozkan M,Fujita Y,Haseda Y,Shimizu M,Kohyama M,Kobiyama K,Eto K,Nabekura J,Horii T,Ishino T,Yuda M,Hemmi H,Kaisho T,Akira S,Kinoshita M,Tohyama K,Yoshioka Y,Ishii KJ,Co

doi

10.1016/j.chom.2014.04.008

subject

Has Abstract

pub_date

2014-05-14 00:00:00

pages

551-63

issue

5

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(14)00142-5

journal_volume

15

pub_type

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