Frontiers in Molecular Biosciences, 2017: Immune-modulating Activity of Hydrogel Microparticles Contributes to the Host Defense in a Murine Model of Cutaneous Anthrax
In prior study, it was shown 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-1a 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-1a, and TNF-a. Consistent with this finding the injection of MPs induced neutrophil influx into footpads, stimulated production of TNF-a
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.
In conclusion, our findings show for the first time that the poly(N-isopropylacrylamide) open-mesh MPs containing copolymerized allylamine or covalently-bound CB dye behave as potent immune stimulators. The dye-coupled MPs were capable of altering the course of infectious disease, and their potency was enhanced by loaded CKs. Detailed examination of the specific roles the immune cell types and their subpopulations, including the DCs, play in the effect of MPs is forthcoming. It will be intriguing to evaluate the effect of MPs with different coupled (surface or external) chemistries against pathogenic bacteria other than B.a. used under different modes of MP administration.