An early response to lipopolysaccharide is the elicitation of macrophages specialized for antigen degradation with negative regulatory effects on the induction of specific immune responses

Abstract

The ability of macrophages to catabolize antigens is relevant both as a means to process complex antigens before presentation to T cells and as a way to down-regulate immune responses by destroying the antigenicity of polypeptides. With these considerations in mind, we investigated the regulation of macrophage catabolic activity by lipopolysaccharide (LPS). Catabolic activity was quantitated by following the distribution and molecular form of 1251-labeled surface components of heat-killed Listeria monocytogenes after their uptake by macrophages. We compared the catabolic activity of macrophages from peritoneal exudates of mice injected intraperitoneally with saline or LPS and found that LPS-elicited macrophages displayed a greatly enhanced (threefold) rate of catabolism. This increase in catabolic activity peaked 3 days after LPS injection and slowly declined thereafter, approaching a base-line level after 3 weeks. The enhancement of catabolic activity was under Lps gene control. Macrophages that were elicited 3 days after intraperitoneal injection of LPS rapidly destroyed the antigenicity of bacterial antigens, expressed low levels of Ia molecules, and processed and presented antigen slowly when tested as antigen-presenting cells in vitro. We also showed that an injection of LPS before infection with L. monocytogenes resulted in diminished development of T-cell reactivity to this organism. These results suggest that LPS elicits a macrophage population specialized for antigen degradation functions, with negative regulatory effects on the induction of specific immune responses.

Intracellular hemolysin-producing Listeria monocytogenes strains inhibit macrophage-mediated antigen processing

“…Trichloroacetic acid (TCA) precipitation was performed on each sample. The amount of radioactivity associated with the soluble and precipitable fractions was determined as described previously (8). In some experiments the number of viable bacteria associated with macrophages was monitored by colony counts (37).…”

In vivo protective effect of lipopolysaccharide against Pseudomonas aeruginosa exotoxin A in mice

“…Contrary to the case of simultaneous LPS and PA administration, LPS treatment prior to PA exposure enhanced the clearance of the labeled PA. The well-established fact that LPS activates the reticuloendothelial system (including macrophages and Kupffer cells) through a whole series of induced mediators (1,3,18) can well explain the enhanced removal of the exotoxin from the various tissues examined. This alone, however, could not explain the increased resistance to PA after LPS treatment, because the amounts of toxin found in the organs of control and LPS-pretreated mice did not differ significantly at any time (Fig.…”

Brucellaouter membrane proteins to control maturation and antigen presentation of mouse dendritic cells

“…The B. abortus 2308 induced apoptosis at different status in macrophages and DCs, which may be related to the different immune types induced by the two host cells and the different interactions between Brucella and the two host cells [52]. Macrophages are full-time phagocytes that engulf and remove exogenous antigens and can expose antigens to the extracellular environment and facilitate host clearance of Brucella [53]. DCs are the main antigen-presenting cells, which process antigens and presents them to the surface of other cells in the immune system.…”