Sterile inflammation induced by Carbopol elicits robust adaptive immune responses in the absence of pathogen-associated molecular patterns

Kate H. Gartlan*, George Krashias, Frank Wegmann, William R. Hillson, Erin M. Scherer, Philip D. Greenberg, Stephanie C. Eisenbarth, Amin E. Moghaddam, Quentin J. Sattentau

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Carbopol is a polyanionic carbomer used in man for topical application and drug delivery purposes. However parenteral administration of Carbopol in animal models results in systemic adjuvant activity including strong pro-inflammatory type-1 T-cell (Th1) polarization. Here we investigated potential pathways of immune activation by Carbopol by comparison with other well-characterized adjuvants. Carbopol administration triggered rapid and robust leukocyte recruitment, pro-inflammatory cytokine secretion and antigen capture largely by inflammatory monocytes. The induction of antigen specific Th1 cells by Carbopol was found to occur via a non-canonical pathway, independent of MyD88/TRIF signaling and in the absence of pattern-recognition-receptor (PRR) activation typically associated with Th1/Ig2a induction. Using multispectral fluorescence imaging (Imagestream) and electron microscopy we demonstrated that phagocytic uptake of Carbopol particles followed by entry into the phagosomal/lysosomal pathway elicited conformational changes to the polymer and reactive oxygen species (ROS) production. We therefore conclude that Carbopol may mediate its adjuvant activity via novel mechanisms of antigen presenting cell activation and Th1 induction, leading to enhanced IgG2a responses independent of microbial pattern recognition.

Original languageEnglish (US)
Pages (from-to)2188-2196
Number of pages9
JournalVaccine
Volume34
Issue number19
DOIs
StatePublished - Apr 27 2016
Externally publishedYes

Keywords

  • Antibodies
  • HIV-1
  • Polyanionic carbomer
  • Th1 immune responses
  • Vaccine adjuvant

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • General Immunology and Microbiology
  • Infectious Diseases
  • Molecular Medicine
  • General Veterinary

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