Immune mimicry in malaria:Plasmodium falciparumsecretes a functional histamine-releasing factor homologin vitroandin vivo

Abstract

The Plasmodium falciparum translationally controlled tumor protein (TCTP) is a homolog of the mammalian histamine-releasing factor (HRF), which causes histamine release from human basophils and IL-8 secretion from eosinophils. Histamine, IL-8, and eosinophils have been reported to be elevated in patients with malaria. This study was undertaken to determine whether malarial TCTP is found in the plasma of malaria-infected patients and to determine whether it has HRF biologic activity. Malarial TCTP was found in lightly infected human volunteers and in heavily infected Malawian children, but not in uninfected patients. Recombinant malarial TCTP, like HRF, stimulated histamine release from basophils and IL-8 secretion from eosinophils in vitro. Whereas malarial TCTP was less active than HRF, the concentrations that were effective in vitro could be achievable in vivo. These data suggest that malarial TCTP, present in human plasma during a malarial illness, may affect host immune responses in vivo.

Rôle de l’histamine et des récepteurs histaminiques dans la pathogenèse du paludisme

“…Par ailleurs, le SYNTHÈSE REVUES TCTP présentant une forte homologie avec le HRF humain a été identifié chez Plasmodium falciparum [22]. Le TCTP de Plasmodium falciparum a pu être mis en évidence dans le plasma de patients infectés et son activité histaminolibératrice sur les basophiles humains a pu être démontrée [23], suggérant que le TCTP de Plasmodium falciparum peut affecter la réponse immunitaire de l'hôte en influant sur les réponses in vivo par sa capacité à libérer l'histamine [23].…”

Cloning and Characterization of a Calcium-binding, Histamine-releasing Protein from Schistosoma mansoni

“…Neither the mechanism of SmTCTP secretion nor its functional significance in host-parasite interaction is fully understood at this time. Given its partial homology with host TCTP it is possible that SmTCTP may play an important role in host modulation similar to the malarial TCTP (21).…”

“…TCTPs from other parasites are also known to possess histamine-releasing function (10,21). Numerous earlier studies, in experimental animals and in patients with acute or chronic schistosomiasis, have reported the release of histamine during infections with S. mansoni (23)(24)(25)(26)(27).…”

Inhibition of Cytokine Gene Transcription by the Human Recombinant Histamine-Releasing Factor in Human T Lymphocytes

“…T he Human recombinant histamine-releasing factor (HrHRF) 3 was originally characterized as an activity found in late phase response fluids from nasal lavages, bronchoalveolar lavage fluids, and skin blister fluids that directly induced histamine release from the basophils isolated from a subpopulation of donors (HrHRF responders) (1). HrHRF was subsequently purified and cloned from 50 liters of culture supernatant collected from the human macrophage cell line U937 (2).…”

“…HrHRF was found to be identical with translationally controlled tumor protein (TCTP; also called p23), a highly and nearly ubiquitously expressed intracellular protein originally isolated from several tumor cell lines (2). Subsequently, homologues of HrHRF/TCTP with mast cell/basophil histamine-releasing activity have been described in the parasites Plasmodium falciparum, Brugia malayi, Wuchereria bancrofti, and Schistosoma mansoni (3)(4)(5).…”