C-reactive protein protects against preerythrocytic stages of malaria

Abstract

We previously reported that low doses of interleukin-1 strongly inhibited in vitro development of the hepatic stages of Plasmodiumfalciparum and P. yoelii. Among several hypotheses, we considered the role of C-reactive protein (CRP), a major acute-phase reactant whose concentration increases markedly in infectious disorders. We demonstrated that human hepatocytes cultured in the presence of interleukin-1 released, as early as 30 min after stimulation, an increased amount of CRP. We then established that CRP bound to the P. falciparum and P. yoelii sporozoite surface membranes, probably via a phosphorylcholine binding site. Experiments in which CRP was added to rat hepatocyte monolayers during or after inoculation confirmed that the target of the CRP-mediated inhibition was at the very early phase of infection. These in vitro functional activities were confirmed in an in vivo model; rats with increased levels of CRP in serum following an injection of turpentine oil were found to be largely protected against an inoculation of P. yoelii sporozoites. The same results were observed in animals inoculated with sporozoites previously incubated in purified CRP or in sera of rats pretreated with turpentine oil. The latter effect was inhibited after incubation of serum from turpentineinjected rats with anti-CRP serum.

Nitric oxide-mediated antiplasmodial activity in human and murine hepatocytes induced by gamma interferon and the parasite itself: enhancement by exogenous tetrahydrobiopterin

“…Both antibodies were a gift from Yupin Charoenvit (Malaria Program, Naval Medical Research Program). Percent parasite inhibition was calculated by comparing the number of schizonts in the experimental cultures with that in controls (= 0% inhibition) (10,11,18,19,(21)(22)(23)(24).…”

Pre‐erythrocytic stages of plasmodia. Role of specific and nonspecific factors

“…Analysis of the time-course indicated that IL-I did not affect maturation of the parasite or the sporozoite itself, but probably had an indirect effect on the very early phase of infection [43]. One of the first hypotheses we proposed to explain IL-1 activity was the secretion of a non specific factor, the C-reactive protein [51]. Results will be given below.…”

“…Participation of such nonspecific factors, e.g. acute-phase proteins, has been postulated to explain the mode of action of IL-I [43,51]. Acute-phase proteins, and particularly the C-reactive protein (CRP), are synthesized at a higher rate when hepatocytes are stimulated with IL-1 [32, 5 I, 52].…”

Haemonchus contortus calreticulin binds to C‐reactive protein of its host, a novel survival strategy of the parasite

“…CRP, also referred as acute phase protein, has binding sites for diverse ligands that contribute to multifunctional properties of the protein. The levels of CRP are enhanced during infection (10), and in many parasitic infections such as the pre‐erythrocytic stages of Plasmodium yoelli (11), Schistosomiasis (12) and Hymenolepes diminuta (13), the elevated CRP was found to be protective. Adult H. diminuta when incubated in CRP containing serum lost motility and showed damaged tegument similar to parasite damage resulting from an immune attack or complement‐mediated lysis.…”