© 2017 Alvarez-Simón et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Exposure to soybean allergens has been linked to asthma outbreaks. Exposure to diesel exhaust particles (DEP) has been associated with an increase in the risk of asthma and asthma exacerbation; however, in both cases the underlying mechanisms remain poorly understood, as does the possible interaction between the two entities. Objective: To investigate how the combination of soybean allergens and DEP can affect the induction or exacerbation of asthma in a murine model. Methods: BALB/c mice received intranasal instillations of saline, 3 or 5 mg protein/ml soybean hull extract (SHE), or a combination of one of these three solutions with DEP. Airway hyperresponsiveness (AHR), pulmonary inflammation in bronchoalveolar lavage, total serum immunoglobulin E and histological studies were assessed. Results: A 5 mg protein/ml SHE solution was able by itself to enhance AHR (p = 0.0033), increase eosinophilic inflammation (p = 0.0003), increase levels of IL-4, IL-5, IL-13, IL-17A, IL-17F and CCL20, and reduce levels of IFN-γ. The combination of 5 mg protein/ml SHE with DEP also produced an increase in AHR and eosinophilic inflammation, but presented a slightly different cytokine profile with higher levels of Th17-related cytokines. However, while the 3 mg protein/ml SHE solution did not induce asthma, co-exposure with DEP resulted in a markedly enhanced AHR (p = 0.002) and eosinophilic inflammation (p = 0.004), with increased levels of IL-5, IL-17F and CCL20 and decreased levels of IFN-γ. Conclusions & clinical relevance: The combination of soybean allergens and DEP is capable of triggering an asthmatic response through a Th17-related mechanism when the soybean allergen concentration is too low to promote a response by itself. DEP monitoring may be a useful addition to allergen monitoring in order to prevent new asthma outbreaks.