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Cell Host Microbe. 2014 May 14;15(5):551-63. doi: 10.1016/j.chom.2014.04.008.

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

Author information

1
Laboratory of Malaria Immunology, Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
2
Laboratory of Vaccine Science, Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation (NIBIO), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
3
Departments of Tropical Medicine and Parasitology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan.
4
Laboratory of Biofunctional Imaging, Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
5
Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation (NIBIO), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
6
Laboratory of Immunochemistry, Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
7
Division of Homeostatic Development Unit, National Institute for Physiological Sciences, 38 Nishigonaka Myodaiji, Okazaki, Aichi 444-8585, Japan.
8
Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
9
Department of Medical Zoology, Mie University School of Medicine, Mie, Tsu 514-0001, Japan.
10
Laboratory of Immune Regulation, Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
11
Laboratory of Host Defense, Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
12
Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan.
13
Laboratory for Nano-neuroanatomy, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan.
14
Laboratory of Malaria Immunology, Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: ccoban@biken.osaka-u.ac.jp.

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.

PMID:
24832450
DOI:
10.1016/j.chom.2014.04.008
[Indexed for MEDLINE]
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