Ehrlichial strategy for survival and proliferation in leukocytes.

Abstract

Ehrlichial organisms classified in the family Rickettsiaceae, are uniquely adapted to survive and proliferate in primary host defensive cells such as monocytes and granulocytes. Recent success in culturing ehrlichial organisms in leukemia cell lines enabled us to apply molecular and cell biologic techniques for their characterization. Ehrlichial major outer membrane protein antigens are encoded by a large number of polymorphic multigenes conserved among related species. Both ligand and receptor for monocytic ehrlichial binding are proteins. For internalization and proliferation of ehrlichial organisms Ca2+-calmodulin and protein tyrosine phosphorylation are required. Monocytic and granulocytic ehrlichial organisms enter and maintain distinct cytoplasmic compartments which do not fuse with each other or lysosomes. Binding of monocytic ehrlichiae to macrophage surface induces rapid protein kinase A activation, leading to interference of signal transduction in the host cells such as Jak-Stat pathway or down regulation of class II antigen in response to interferon-γ. Altogether ehrlichial organisms upon contact with phagocytic leukocytes maim multiple innate microbicidal activity directed to them.