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Infection and Immunity, September 2001, p. 5270-5277, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5270-5277.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Potent Stimulation of the Innate Immune System by a Leishmania brasiliensis Recombinant Protein

Monamaris M. Borges,1 Antonio Campos-Neto,2,3,* Paul Sleath,4 Keneth H. Grabstein,4 Philip J. Morrissey,5 Yasir A. W. Skeiky,4 and Steven G. Reed2,4

Instituto Butantan, São Paulo,1 and Medical School of Itajubá, Minas Gerais,3 Brazil; Infectious Disease Research Institute2 and Corixa Corporation,4 Seattle, Washington 98104; and Immunex Corporation, Seattle, Washington 981015

Received 7 March 2001/Returned for modification 2 May 2001/Accepted 20 June 2001

The interaction of the innate immune system with the microbial world involves primarily two sets of molecules generally known as microbial pattern recognition receptors and microbial pattern recognition molecules, respectively. Examples of the former are the Toll receptors present particularly in macrophages and dendritic cells. Conversely, the microbial pattern recognition molecules are conserved protist homopolymers, such as bacterial lipopolysaccharides, lipoteichoic acids, peptidoglycans, glucans, mannans, unmethylated bacterial DNA, and double-strand viral RNA. However, for protists that lack most of these molecules, such as protozoans, the innate immune system must have evolved receptors that recognize other groups of microbial molecules. Here we present evidence that a highly purified protein encoded by a Leishmania brasiliensis gene may be one such molecule. This recombinant leishmanial molecule, a homologue of eukaryotic ribosomal elongation and initiation factor 4a (LeIF), strongly stimulates spleen cells from severe combined immunodeficient (SCID) mice to produce interleukin-12 (IL-12), IL-18, and high levels of gamma interferon. In addition, LeIF potentiates the cytotoxic activity of the NK cells of these animals. Because LeIF is a conserved molecule and because SCID mice lack T and B lymphocytes but have a normal innate immune system (normal reticuloendothelial system and NK cells), these results suggest that proteins may also be included as microbial pattern recognition molecules. The nature of the receptor involved in this innate recognition is unknown. However, it is possible to exclude the Toll receptor Tlr4 as a putative LeIF receptor because the gene encoding this receptor is defective in C3H/HeJ mice, the mouse strain used in the present studies.

* Corresponding author. Mailing address: Infectious Disease Research Institute, 1124 Columbia St., Suite 600, Seattle, WA 98104. Phone: (206) 381-0883. Fax: (206) 381-3678. E-mail: acampos{at}idri.org.

Infection and Immunity, September 2001, p. 5270-5277, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5270-5277.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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