Suppression ofPlasmodium cynomolgiin Rhesus Macaques by Coinfection withBabesia microti

Abstract

Both Plasmodium and Babesia species are intraerythrocytic protozoans that infect a wide range of hosts, including humans, and they elicit similar inflammatory responses and clinical manifestations that differ markedly in severity. We recently reported that a rhesus macaque that was chronically infected with Babesia microti was able to control infection with Plasmodium cynomolgi (a parasite of macaques with characteristics very similar to those of Plasmodium vivax) better than naïve monkeys. To confirm this and to investigate the underlying immunopathology, six naïve rhesus monkeys were infected with B. microti. After 24 days, four of these monkeys and four naïve rhesus monkeys were challenged with P. cynomolgi blood-stage parasites. B. microti persisted at low levels in all monkeys, and the clinical parameters were comparable to those of noninfected controls. There was a significant decrease in P. cynomolgi parasitemia in animals coinfected with B. microti compared to the parasitemia in animals infected with P. cynomolgi alone. This decrease in P. cynomolgi parasitemia correlated with increases in the levels of proinflammatory monocytes at the time of P. cynomolgi infection and with higher C-reactive protein (CRP) serum levels 1 week after malaria infection. Therefore, we conclude that ongoing infection with B. microti parasites leads to suppression of malaria infection.

Experimental transfusion‐induced Babesia microti infection: dynamics of parasitemia and immune responses in a rhesus macaque model

“…Innate responses such as monocyte activation have been reported upon infection of monkeys with B. microti . Another study reported higher frequency of IL‐10–producing B cells (Bregs) and CD4+CD25+FoxP3+ T cells during the course of B. microti infection in mice .…”

Hemoparasites in a wild primate: Infection patterns suggest interaction of Plasmodium and Babesia in a lemur species

“…The suppression of malaria infections in the course of ongoing babesiosis has been investigated in rhesus macaques ( Macaca mulatta ) in laboratory settings ( van Duivenvoorde et al., 2010 ), after it was found that a macaque infected with a B. microti -like parasite showed a suppressed Plasmodium cynomolgi infection ( Wel et al., 2008 ). Heterologous immunity between the two parasites has also been observed in mice ( Cox, 1978 , Zivkovic et al., 1984 ).…”

“…Heterologous immunity between the two parasites has also been observed in mice ( Cox, 1978 , Zivkovic et al., 1984 ). It has been proposed that the cross-protection is most likely due to immune responses such as the activation of a distinct class of pro-inflammatory monocytes, release of pro-inflammatory cytokines, and increased C-reactive protein levels, which potentially play an important protective role in malaria infections ( Clark, 2001 , Ansar et al., 2006 , van Duivenvoorde et al., 2010 ). It has also been proposed that this heterologous immunity might be exploited for the development of malaria vaccines.…”

Human babesiosis, an emerging tick-borne disease in the People’s Republic of China

“…In 2005, Lobo et al reported that B. divergens and P. falciparum use the common receptors, glycophorins A and B, to invade the human erythrocyte [ 23 ]. Duivenvoorde LM et al reported that a rhesus macaque chronically infected with B. microti was able to control the infection with P. cynomolgi better than naïve monkeys [ 24 ]. The suppression of a Plasmodium infection after chronic exposure to B. microti warrants further investigation for a possible protective role of Babesia infection on Plasmodium .…”