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Infection and Immunity, March 2000, p. 1183-1188, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Malaria Infection Induces Rapid Elevation of the Soluble Fas Ligand Level in Serum and Subsequent T Lymphocytopenia: Possible Factors Responsible for the Differences in Susceptibility of Two Species of Macaca Monkeys to Plasmodium coatneyi Infection

Jun Matsumoto,1,* Satoru Kawai,1 Keiji Terao,2 Masashi Kirinoki,1 Yasuhiro Yasutomi,3 Masamichi Aikawa,4 and Hajime Matsuda1

Department of Medical Zoology, Dokkyo University School of Medicine, Tochigi,1 Tsukuba Primate Center for Medical Sciences, Ibaraki,2 Department of Bioregulation, Mie University School of Medicine, Mie,3 and Research Institute of Medical Sciences, Tokai University, Kanagawa,4 Japan

Received 14 September 1999/Returned for modification 4 November 1999/Accepted 15 November 1999

The intraerythrocytic stage of the simian malaria parasite Plasmodium coatneyi (CDC strain) was intravenously inoculated into two species of macaques with different susceptibilities to infection with this parasite, including four Japanese macaques (Macaca fuscata) and three cynomolgus macaques (M. fascicularis). The Japanese macaques infected with P. coatneyi developed severe clinical manifestations similar to those of severe human malaria and eventually became moribund, while the infected cynomolgus macaques, natural hosts of the parasite, exhibited no severe manifestation of disease except anemia and finally recovered from the infection. In the infected Japanese macaques, peripheral CD4+ and CD8+ T-cell populations were markedly decreased and fragmentation of chromosomal DNA in peripheral blood mononuclear cells was detected during the terminal period of infection, suggesting that apoptotic cell death was responsible at least in part for the T lymphocytopenia. Furthermore, soluble Fas ligand levels in sera of the infected Japanese macaques increased gradually to a markedly high level of 28.83 ± 10.56 pg/ml (n = 4) when the animals became moribund. On the other hand, none of the infected cynomolgus monkeys exhibited either T lymphocytopenia or elevated soluble Fas ligand level. These findings suggest that differences in immune response between the two species of macaque tested accounted for the contrasting outcomes after infection with the same isolate of malarial parasite, and in particular that a profound T lymphocytopenia due to Fas-derived apoptosis played a role in the fatal course of malaria in the infected Japanese macaques.

* Corresponding author. Mailing address: Department of Medical Zoology, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan. Phone: (81) 282-87-2134. Fax: (81) 282-86-6431. E-mail: junmatsu{at}dokkyomed.ac.jp.

Infection and Immunity, March 2000, p. 1183-1188, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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