Chemokine-Releasing Microparticles Improve Bacterial Clearance and Survival of Anthrax Spore-Challenged Mice

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dc.contributor.authorPopova, Taissia G.
dc.contributor.authorTeunis, Allison
dc.contributor.authorEspina, Virginia
dc.contributor.authorLiotta, Lance
dc.contributor.authorPopov, Serguei G.
dc.date.accessioned2018-08-07T16:11:19Z
dc.date.available2018-08-07T16:11:19Z
dc.date.issued2016-09-15
dc.description.abstractIn this study the hydrogel microparticles (MPs) were used to enhance migration of neutrophils in order to improve outcome of anthrax infection in a mouse model. Two MP formulations were tested. In the first one the polyacrylamide gel MPs were chemically coupled with Cibacron Blue (CB) affinity bait. In the second one the bait molecules within the MPs were additionally loaded with neutrophil-attracting chemokines (CKs), human CXCL8 and mouse CCL3. A non-covalent interaction of the bait with the CKs provided their gradual release after administration of the MPs to the host. Mice were challenged into footpads with Bacillus anthracis Sterne spores and given a dose of MPs a few hours before and/or after the spores. Pre-treatment with a single dose of CK-releasing MPs without any additional intervention was able to induce influx of neutrophils to the site of spore inoculation and regional lymph nodes correlating with reduced bacterial burden and decreased inflammatory response in footpads. On average, in two independent experiments, up to 53% of mice survived over 13 days. All control spore-challenged but MP-untreated mice died. The CB-coupled particles were also found to improve survival likely due to the capacity to stimulate release of endogenous CKs, but were less potent at decreasing the inflammatory host response than the CK-releasing MPs. The CK post-treatment did not improve survival compared to the untreated mice which died within 4 to 6 days with a strong inflammation of footpads, indicating quick dissemination of spores though the lymphatics after challenge. This is the first report on the enhanced innate host resistance to anthrax in response to CKs delivered and/or endogenously induced by the MPs.
dc.description.sponsorship1R21AI117425-01 from the National Institutes of Health, USA (SP VE and LL)
dc.identifier.citationPopova, Taissia G., Allison Teunis, Virginia Espina, Lance A. Liotta, and Serguei G. Popov. “Chemokine-Releasing Microparticles Improve Bacterial Clearance and Survival of Anthrax Spore-Challenged Mice.” PLOS ONE 11, no. 9 (September 15, 2016): e0163163. https://doi.org/10.1371/journal.pone.0163163.
dc.identifier.doi10.1371/journal.pone.0163163
dc.identifier.urihttps://hdl.handle.net/1920/11075
dc.language.isoen_US
dc.publisherPLOS
dc.rightsAttribution 3.0 United States
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/us/
dc.subjectNeutrophils
dc.subjectBacterial spores
dc.subjectInflammation
dc.subjectMouse models
dc.subjectAnthrax
dc.subjectImmune Response
dc.subjectInflammatory diseases
dc.subjectImmune cells
dc.titleChemokine-Releasing Microparticles Improve Bacterial Clearance and Survival of Anthrax Spore-Challenged Mice
dc.typeArticle

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