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Coinfection with Nonlethal Murine Malaria Parasites Suppresses Pathogenesis Caused by Plasmodium berghei NK65

Mamoru Niikura^1,*,, Shigeru Kamiya, Kiyoshi Kita and Fumie Kobayashi^1,

^* Institute of Laboratory Animals, Graduate School of Medicine and Department of Infectious Diseases, Faculty of Medicine, Kyorin University, Tokyo; and Department of Biomedical Chemistry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

Mixed infection with different Plasmodium species is often observed in endemic areas, and the infection with benign malaria parasites such as Plasmodium vivax or P. malariae has been considered to reduce the risk of developing severe pathogenesis caused by P. falciparum. However, it is still unknown how disease severity is reduced in hosts during coinfection. In the present study, we investigated the influence of coinfection with nonlethal parasites, P. berghei XAT (Pb XAT) or P. yoelii 17X (Py 17X), on the outcome of P. berghei NK65 (Pb NK65) lethal infection, which caused high levels of parasitemia and severe pathogenesis in mice. We found that the simultaneous infection with nonlethal Pb XAT or Py 17X suppressed high levels of parasitemia, liver injury, and body weight loss caused by Pb NK65 infection, induced high levels of reticulocytemia, and subsequently prolonged survival of mice. In coinfected mice, the immune response, including the expansion of B220^intCD11c⁺ cells and CD4⁺ T cells and expression of IL-10 mRNA, was comparable to that in nonlethal infection. Moreover, the suppression of liver injury and body weight loss by coinfection was reduced in IL-10^–/– mice, suggesting that IL-10 plays a role for a reduction of severity by coinfection with nonlethal malaria parasites.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Fumie Kobayashi and Dr. Mamoru Niikura, Faculty of Medicine, Kyorin University, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan. E-mail addresses: fumfum{at}ks.kyorin-u.ac.jp and mniikura{at}ks.kyorin-u.ac.jp

² Abbreviations used in this paper: Pb, Plasmodium berghei; Py, Plasmodium yoelii; pRBC, parasitized RBC; AST, aspartic aminotransferase; ALT, alanine aminotransferase.