Suppression of Ia antigen expression on gamma interferon treated macrophages infected with Ehrlichia risticii

Abstract

Ehrlichia risticii is an obligate intracellular bacterium of monocytes/macrophages. In this report, using immunofluorescence staining, flow cytometry, and Kolmogorov-Smirnov analysis of histograms, the response of P338D 1 and peritoneal macrophages stimulated with recombinant murine interferon-γ (rIFN-γ) was examined for the expression of major histocompatibility complex Class II gene product (Ia) and effect of E. risticii infection on induction of Ia surface expression. Maximal expression of Ia by sham-infected P388D 1 cells was observed 2 days post rIFN-γ addition followed by a progressive decline. These stimulatory effects of rIFN-γ were dose dependent. Relative to sham-infected P388D 1 cells, the induction of Ia by rIFN-γ (200 U ml −1) on E. risticii-infected P388D 1 cells was significantly suppressed at each time point tested through Day 5 with maximal suppression of 88% occurring on Day 2. Similarly, the induction of Ia by rIFN-γ on E. risticii-infected peritoneal macrophages was significantly suppressed by 77% (fluorescent microscopy) when compared to sham-infected peritoneal macrophages. The higher dose of rIFN-γ (2000 U ml −1) failed to restore Ia surface expression by E. risticii-infected P388D 1 cells. The suppression of Ia on P388D 1 cells in response to RIFN-γ was not related to the degree of infection of these cells by E. risticii. A soluble inhibitor substance was not demonstrable in the supernatant from E. risticii-infected cells, nor were inhibitor levels of prostaglandin E 2 levels found in the supernatant. Suppression of surface Ia expression on the macrophage suggests a mechanism whereby I. risticii may evade T-lymphocyte recognition, hinder antigen-specific T-lymphocyte activation, and promote their own survival.