The DC subsets that express αE integrin (CD103) have been described to exert antagonistic functions, driving T cells towards either an inflammatory (Th1/Th17) or immunosuppressive phenotype (regulatory T cells - Treg). These functions depend on the tissue they reside and microenvironment factors or stimuli that this Antigen-presenting cell (APC) subpopulation receive. In this regard, immunoregulatory phenotype has been described in small subsets of CD103+ DCs from lung and intestinal mucosa. The function of this APC subpopulation in pulmonary Paracoccidioides brasiliensis infection is poorly described. Here, we showed that lung CD103+ DCs contribute to Treg differentiation in a pulmonary P. brasiliensis infection model, which was attributed to downregulation of costimulatory molecules analyzed in these APC subtypes 21 days post-infection. Overall, this data suggests that P. brasiliensis infection caused an immunosuppression that has also been observed in patients with the most severe form of Paracoccidioidomycosis (PCM) – a sickness caused by this fungus genus. Furthermore, these results open new perspectives for knowledge of the mechanisms that underlie the higher percentage of Treg cells found in peripheral blood of PCM patients.