Immune mimicry in malaria: Plasmodium falciparum secretes a functional histamine-releasing factor homolog in vitro and in vivo

doi:10.1073/pnas.201191498

Immune mimicry in malaria: Plasmodium falciparum secretes a functional histamine-releasing factor homolog in vitro and in vivo

Divisions of ^*Allergy and Clinical Immunology and ^§Clinical Pharmacology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD 21224; ^‡Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48104; ^¶Malaria Research Project and Wellcome Trust Research Laboratories, Queen Elizabeth Central Hospital, Blantyre, Malawi; ^‖Department of Medicine, University of Melbourne, Parkville 3050, Australia; and ^**Department of Internal Medicine, College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824

Edited by Anthony Cerami, The Kenneth S. Warren Laboratories, Tarrytown, NY, and approved July 24, 2001 (received for review April 18, 2001)

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.

Footnotes

↵ † To whom reprint requests should be addressed. E-mail: smacdona{at}mail.jhmi.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

HRF,

histamine-releasing factor;

TCTP,

translationally controlled tumor protein