The prevalence of Mycobacterium abscessus infections in non-cystic fibrosis (CF) patients has increased in recent years. In this study, we investigate whether immune defects explain the apparent susceptibility to this opportunistic infection in non-CF patients.We performed stimulations of peripheral blood mononuclear cells and whole blood from 13 patients with M. abscessus pulmonary disease and 13 healthy controls to investigate their cytokine production after 24 h and 7 days.Patients were predominantly women (54%) with a mean age of 59 years; 62% had nodular bronchiectatic disease. Many patients had predisposing pulmonary diseases, such as COPD (46%), and asthma (23%). Patients with COPD showed an impaired interleukin (IL)-6 response to M. abscessus and a reduced IL-17 response to Candida, together with a M. abscessus-specific enhanced IL-22 production. Patients without COPD showed higher levels of interleukin-1 receptor antagonist (IL-1Ra), an anti-inflammatory molecule. Within the non-COPD patients, those with bronchiectasis showed defective interferon (IFN)-γ production in response to Candida albicans.In conclusion, susceptibility to M. abscessus is likely determined by a combination of immunological defects and predisposing pulmonary disease. The main defect in the innate immune response was a shift of the ratio of IL-1β to IL-1Ra, which decreased the bioactivity of this pathway in the adaptive immune response. In the adaptive immune response there was defective IL-17 and IFN-γ production. Patients with COPD and bronchiectasis showed different cytokine defects. It is therefore crucial to interpret the immunological results within the clinical background of the patients tested.