Topical Application of the Quaternary Ammonium Compound Didecyldimethylammonium Chloride Activates Type 2 Innate Lymphoid Cells and Initiates a Mixed-Type Allergic Response.

Abstract

Didecyldimethylammonium chloride (DDAC) is an antimicrobial dialkyl-quaternary ammonium compound used in industrial and commercial products. Clinical data suggest that DDAC exposure elicits multiple types of hypersensitivity reactions; here, we confirm this observation in a BALB/c murine model. To examine the immunological mechanism behind this mixed-type response and the potential involvement of type 2 innate lymphoid cells (ILC2s), we assessed early immune responses in the skin following topical DDAC exposure (0.125% and 0.5%). DDAC exposure resulted in a rapid and dramatic increase in the Th2-skewing and ILC2-activating cytokine thymic stromal lymphopoietin. Correspondingly, dermal ILC2s were activated 24 h after DDAC exposure, resulting in increased expression of CD25, ICOS and KLRG1, and decreased CD127 throughout 7 days of exposure. Following ILC2 activation, the Th2 cytokine IL-4 was elevated compared with control mice in total ear protein lysate (0.5% DDAC). Rag2-/- mice were used to determine a functional role for ILC2s in DDAC-induced sensitization. ILC2s from Rag2-/- mice were similarly activated by DDAC and, importantly, produced significant levels of IL-4 and IL-5 in the skin (0.5% DDAC). These data indicate that ILC2s contribute to early Th2 immune responses following DDAC exposure. ILC2s have been previously implicated in allergic responses, but to our knowledge have not been thoroughly investigated in chemical sensitization. These results indicate that following DDAC exposure, skin ILC2s become activated and produce Th2 cytokines, providing a possible mechanism for the development of the mixed-type allergic responses commonly observed with chemical sensitizers.