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Parasite 2, 31-39 54 Mohammed, S.R. and Faubert, G.M. (1995) Disaccharidase deficiencies in Mongolian gerbils (Meriones unguiculatus) protected against Giardia lamblia. Pm'asitol. Res. 81,582-590 55 Leitch, G.J. el al. (1993) Effect of protein malnutrition on experimental giardiasis in the Mongolian gerbils. Scand. ]. Gastro- entelvl. 28, 885-893 56 Di Prisco, M.C. et al. (1993) Possible relationship between allergic disease and infection by Giardia lamblia. Aml. A/lecky 70, 210-213 57 Xiao, L. (1994) Giardia infection in farm animals. Parasitology Today 10, 436-438 Modulation of Host Cell lntracellular Ca z+ M. Olivier During the course of evolution, protozoan parasites have de- veh,ped stratc~ies to subvert the irmm:ne response of their host in order to multiply, reproduce and surv;ve. One of theqe inherited strategies is their capacity to mc,dulate the host cell transductional mechanisms in their flwor. Alteration of host cells Ca 2- homt'ostasis following interaction and/or ira,asian lnt protozoan parasites such as Leishmania donovani, Trypanosorna cruzi, Plasmodium falciparum or Entamoeba histolytica has been reported. There is diwct evidence that such disturbances my responsible for pathge, enesis observed during parasitic irrfections. This homeostatic imbalance of Ca'- ~ irr tlte host cell is art early ii:ducible event whose un&rhting mechanisms needs further investigation, as discussed here by Martin Olivier. Numerous potentially deadly intracellular pathogens including Leishmania ~-.~, Yersinia ~ and HIV ~ can pro- mote mononuclear phagocyte dysfunctions. Inhibition of the ability of these cells to develop an effective im- mune response mav favor persistent infection. It has been reported that host cell dysfunctions ~--~following their infection with intracellular protozoan can be related to abnormal intracellular Ca 2+ concentration ([Ca2+ ]i) homeostasis. Induction of Ca 2~- mobilization in host cells follow- ing initial contact with various pathogens and its implication in the penetration or internalization of parasites is well described, and has recently been reviewed by Docampo and Moreno 6. in the present Martin Olivier is at the Centce de Rechecche en Infectiologie, 9500, Centre Hospitalier de I'Universit6 Laval, and Ddpactement de Microbiologie, Facult6 de Mddecine, Univecsitd Laval, 2705 boulevard Laurier, Ste-Foy, Qudbec, Canada G IV 4G2. Tel" +1 418 654 2705, Fax: +1 418 654 2715, e-maih MOlivier@VM I .ULavaI.CA Parasitology Today, vol. 12, no. 4, 1996 co>,,eh~ o ~ 9~6. E ....... - s..... ~ L:d review, the effe :ts of sustained alteration of the Ca 2" homeostatic b, ~ance on the host cell functionability is emphasized. Alteration of signaling To develop an effective cell-mediated immune re- sponse, infected macrophages must be able to induce activation of T cells in a specific manner. In turn, T cells can activate macrophages for cytocidal func- tions:-" by secreting lymphokines. The importance of lymphokine secretion by T cells in the control of in- fection by Leishmania donovani has been shown by several investigators 7.1"-13. Macrophage-T-cell inter- actions are fundamental to cell-mediated immunity, aim the participation of macrophages is crucial for its initiation and support. Infection of mononuclear phagocytes with Leishmania leads to the inhibition of many of their functions, including phagocytosis 14, the production of interleukin 1 (IL-1), expression of the c-los gene in response to lipopolysaccharide (LPS) and phorbol este-c~, the expression of the major histocornpatibility complex (MHC) class II molecule in response to interferon gamma (IFN-~), and the generation of oxy- gen radicals following stimulation with the chemo- tactic peptide fMLP (fMet-Leu-Phe) or phorbol ester (reviewed in Ref. 3). Signal transduction that utilizes Ca'- ~ and/or pro- tein kinase C (PKC) as second messengers are deficient in human monocytes infected with L. donovani ~2. PKC specific activity and its translocation from the cytosol to the membrane (Fig. 1), an important step in signal transduction in response to phorbol esters, are signifi- cantly reduced. This inhibition is reflected by a de- crease in both phosphorylation events and generation (ff oxygen radicals. This defective signal transduction