Prior Exposure to Ortho-Phthalaldehyde Augments IgE-Mediated Immune Responses to Didecyldimethylammonium Chloride: Potential for 2 Commonly Used Antimicrobials to Synergistically Enhance Allergic Disease

Abstract

Abstract Health-care workers have an increased incidence of allergic disease compared with the general public and are exposed to a variety of high-level disinfectants. Although exposure to these agents has been associated with allergic disease, findings between epidemiology and animal studies often conflict respecting immunological mechanisms. Therefore, we hypothesized that previous exposure to a representative IgE-mediated sensitizer (ortho-phthalaldehyde [OPA]) alters immune responses to a representative T-cell-mediated sensitizer (didecyldimethlyammonium chloride [DDAC]). Here, BALB/c mice were topically exposed to OPA (0.5%) for 3 days, rested, then topically exposed to DDAC (0.0625%, 0.125%, and 0.25%) for 14 days. Coexposure resulted in phenotypic changes in draining lymph node (dLN) cells, including a decreased frequency of CD8+ T cells and increased frequency and number of B cells compared with DDAC-only treated mice. The coexposed mice also had enhanced Th2 responses, including significant alterations in: dLN Il4 (increased), B-cell activation (increased), CD8+ T-cell activation (decreased), and local and systemic IgE production (increased). These changes were not observed if mice were exposed to DDAC prior to OPA. Exposure to OPA alone shows Th2 skewing, indicated by increased activation of skin type 2 innate lymphoid cells, increased frequency and activation of draining lymph node B cells, and increased levels of type 2 cytokines. These findings suggest that the OPA-induced immune environment may alter the response to DDAC, resulting in increased IgE-mediated immune responses. This data may partially explain the discordance between epidemiological and laboratory studies regarding disinfectants and provide insight into the potential immunological implications of mixed chemical exposures.