Epidemic typhus is an acute human disease caused by the obligate intracellular Gram-negative bacterium, Rickettsia prowazeki. R. prowazeki multiplies within endothelial cells lining the capillaries and can also grow within the macrophages of the host. Experimental evidence indicates that both cell-mediated and humoral immunity are protective against R. prowazeki, but the mechanisms of protection have not been delineated. We have discovered a species-specific lymphokine able to prevent rickettsial growth in both macrophages and fibroblasts. We will determine how the survival and growth of R. prowazeki in nonprofessional (fibroblasts and endothelial cells) and professional (macrophages and monocytes) phagocytes is modulated by lymphokines and specific antibodies. Specifically: I. The influence of lymphokines on the interaction of R. prowazeki with nonprofessional and professional phagocytes will be defined and characterized by investigation of (A) the ability of human lymphokines to inhibit the growth of R. prowazeki in human vascular endothelial cells, and to cause cytotoxicity in combination with R. prowazeki in human monocytes and macrophages, (B) the mechanism of mouse lymphokine-induced suppression of the growth of R. prowazeki in a mouse fibroblast cell line, (C) the mechanism of the cytotoxicity caused by the combination of R. prowazeki and mouse lymphokines in a mouse macrophage-like cell line, and (D) the nature of the anti-rickettsial factor(s) in mouse lymphokine preparations. II. The effects of specific antibodies on the interaction of R. prowazeki with nonprofessional and professional phagocytes will be characterized by investigation of (A) the mechanism by which IgG prevents infection of a mouse fibroblast line with R. prowazeki, and the applicability of this information to human vascular endothelial cells, and (B) the mechanism of IgG-mediated destruction of R. prowazeki in a mouse macrophage-like cell line, and the applicability of this information to human monocytes and human monocyte-derived macrophages.
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