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Sci Immunol. 2017 Jun 2;2(12). pii: eaam8093. doi: 10.1126/sciimmunol.aam8093.

Plasmodium products persist in the bone marrow and promote chronic bone loss.

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 Host Defense, IFReC, Osaka University, Suita, Osaka 565-0871, Japan.
3
Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
4
Leiden Malaria Research Group, Department of Parasitology, Leiden University Medical Centre, 2333 ZA Leiden, Netherlands.
5
Division of Pediatric Infectious Diseases, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaboration Innovation Centre, Chengdu 610041, China.
6
Laboratory of Vaccine Science, IFReC, Osaka University, Suita, Osaka 565-0871, Japan.
7
Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
8
Laboratory of Malaria Immunology, Immunology Frontier Research Center (IFReC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. ccoban@biken.osaka-u.ac.jp.

Abstract

Although malaria is a life-threatening disease with severe complications, most people develop partial immunity and suffer from mild symptoms. However, incomplete recovery from infection causes chronic illness, and little is known of the potential outcomes of this chronicity. We found that malaria causes bone loss and growth retardation as a result of chronic bone inflammation induced by Plasmodium products. Acute malaria infection severely suppresses bone homeostasis, but sustained accumulation of Plasmodium products in the bone marrow niche induces MyD88-dependent inflammatory responses in osteoclast and osteoblast precursors, leading to increased RANKL expression and overstimulation of osteoclastogenesis, favoring bone resorption. Infection with a mutant parasite with impaired hemoglobin digestion that produces little hemozoin, a major Plasmodium by-product, did not cause bone loss. Supplementation of alfacalcidol, a vitamin D3 analog, could prevent the bone loss. These results highlight the risk of bone loss in malaria-infected patients and the potential benefits of coupling bone therapy with antimalarial treatment.

PMID:
28783657
DOI:
10.1126/sciimmunol.aam8093

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