Lipopolysaccharide-like molecules derived from Wolbachia endobacteria of the filaria Onchocerca volvulus are candidate mediators in the sequence of inflammatory and antiinflammatory responses of human monocytes

The majority of Onchocerca volvulus-infected persons show signs of cellular anergy, and long-time survival of adult and larval parasites in subcutaneo us tissue is observed. The mechanisms leading to immunological hyporesponsi veness are poorly understood. Monocytesimacrophages represent a link betwee n the innate and acquired immune system and are candidate cells to promote inflammatory and antiinflammatory processes. In the present study we have s hown that products of microfilarial (O. volvulus) and adult (O. volvulus an d O. ochengi) parasites affect monocytes in vitro. An early production of T NF-a by exposed monocytes was followed by the production of IL-10 and a red uced expression of HLA-BR and the costimulatory molecules B7-1 and B7-2, wh ile other adhesion receptors remained unaffected. Downregulation of the fun ctional membrane receptors failed to occur after treatment of the cells wit h anti-IL-10 antibodies. The engagement of CD 14, a dominant: membrane rece ptor on monocytes and major binding protein for lipopolysaccharides, was in dicated by partial blocking of monocyte modulation by neutralizing antibodi es to CD 14 and by the antagonistic lipid A analog compound 406. Lipopolysa ccharide-like molecules were detected in sterile products of O. volvulus st ages which could originate from Wolbachia bacteria related to Gram-negative Rickettsiales, known to be abundant in the hypodermis and the female repro ductive organs of O. volvulus. The present results indicate that the monocy te/macrophage may be a major target cell for immunomodulatory parasite-deri ved and intraparasitic, bacteria-derived molecules, thereby contributing to the host's cellular hyporesponsiveness. (C) 2000 Editions scientifiques et medicales Elsevier SAS.