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Abstract
We recently reported that the open-mesh (0.7 μ) polyacrylamide microparticles (MPs) with internally-coupled Cibacron affinity dye demonstrate protective effect in mice challenged into footpads with high doses (200 LD50) of anthrax (Sterne) spores. A single injection of MPs before spore challenge reduces inflammatory response, delays onset of mortality and promotes survival. In this study, we show that the effect of MPs was substantially increased at the lower spore dose (7 LD50). The inflammation of footpads was reduced to the background level, and 60% of animals survived for 16 days while all untreated infected animals died within 6 days with strong inflammation. The effects of MPs were promoted when the MPs were loaded with a combination of neutrophil-attracting chemokines IL-8 and MIP-1α which delayed the onset of mortality in comparison with untreated mice for additional 8 days. The MPs were not inherently cytotoxic against the bacteria or cultured murine Raw 264.7 cells, but stimulated these cells to release G-CSF, MCP-1, MIP-1α, and TNF-α. Consistent with this finding the injection of MPs induced neutrophil influx into footpads, stimulated production of TNF-α associated with migration of pERK1/2-positive cells with the Langerhans phenotype from epidermis to regional lymph nodes. Our data support the mechanism of protection in which the immune defense induced by MPs along with the exogenous chemokines counterbalances the suppressive effect caused by anthrax infection.
Highlights
Engineered nano- and micro-particles (MPs) find a fast-growing variety of applications in industry, biology, and medicine
We found that the pretreatment of anthrax spore-challenged mice with chemokine-loaded MPs (CK-MPs) improved bacterial clearance and survival (Popova et al, 2016)
We previously studied the biological properties of hydrogel MPs in mice subcutaneously challenged with a lethal dose of anthrax spores
Summary
Engineered nano- and micro-particles (MPs) find a fast-growing variety of applications in industry, biology, and medicine. Some types of MPs display their effects through direct interaction with the pathogen while others are capable of inducing protection of the host against infection indirectly through stimulation or suppression of the immune cell responses (Look et al, 2010; Qasim et al, 2014; Gupta et al, 2016). MPs are capable of targeting different cells types present in tissues contacting with the external. One of the most likely biologically relevant MP targets are dendritic cells (DCs) due to a number of key DC properties, such as, their capacity to internalize foreign particles, transport them to lymph nodes, and present the associated antigens to other immune cells. The capacity of MPs to induce immune response or enhance presentation of MP-loaded antigens made them popular candidates as vaccine adjuvants. Adjuvants induce recruitment of various immune cells to the site of injection, some of which traffic the antigen to the draining lymph nodes to induce specific immune responses (Mosca et al, 2008; McKee et al, 2009)
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