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

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.

journal_name

Vaccine

journal_title

Vaccine

authors

Gartlan KH,Krashias G,Wegmann F,Hillson WR,Scherer EM,Greenberg PD,Eisenbarth SC,Moghaddam AE,Sattentau QJ

doi

10.1016/j.vaccine.2016.03.025

subject

Has Abstract

pub_date

2016-04-27 00:00:00

pages

2188-96

issue

19

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(16)00336-4

journal_volume

34

pub_type

杂志文章

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