Adaptive Immune Response to <i>Mycobacterium abscessus</i> Complex and Cross-Reactivity of BCG Vaccination

Abstract

Background: Mycobacterium abscessus complex (MABSC) is a major pathogenic group among nontuberculous mycobacteria (NTM). Here we characterized the adaptive immune response to MABSC and its cross reactivity with Mycobacterium bovis (Bacille Calmette-Guerin, BCG) using cystic fibrosis (CF) lung infection as a model. Methods: This was a cross-sectional study enrolling CF patients with and without history of NTM infection (CF/NTM+ and CF/NTM-), non-CF controls vaccinated and not vaccinated with BCG (C/BCG+ and C/BCG-). The anti-MABSC response was assessed in terms of lymphocyte activity and cytokine production after challenge with MABSC, and measurement of specific IgG. Results: The CF/NTM+ and C/BCG+ groups had cellular and cytokine responses with similar intensity, characterized by a Th1-dominated phenotype – high CD4 T-cell proliferation, increased IFN-γ and TNF-α production. The B-cell response and its associated cytokines CD40L and IL-4 were less pronounced, although IgG levels were higher in the CF/NTM+ group than in controls. Proliferating lymphocytes, increased IFN-γ and TNF-α production were also observed in part of the individuals of the CF/NTM- and C/BCG- groups, indicating environmental exposure, undetected or past infection. IL-2 increased only in the CF groups and may be specifically linked to the anti-MABSC response. Altogether, BCG-vaccinated individuals (CF and non-CF) had higher lymphocyte proliferation intensity than the non-vaccinated ones. Conclusion: The anti-MABSC response follows a pattern seen in other mycobacterial infections. BCG vaccination provides a cross-reactive response against MABSC and can have potential to mitigate the pathology of NTM infections. The potential of cytokine measurement for diagnosing MABSC infection is under investigation. Funding Information: RMM was granted a fellowship by the Sao Paulo Research Foundation (FAPESP, grant reference #2019/14134-5) and the study received funds from the Cystisk Fibrose Foreningen (Danish Cystic Fibrosis Association). Declaration of Interests: The authors have no conflicts of interests to declare. Ethics Approval Statement: The study was approved by the Regional Scientific Ethical Committees, Denmark (VEK, RH-19022288) and was in accordance with the Declaration of Helsinki and guidelines from the Danish Data Protection Agency. All participants signed a written informed consent, confirming their voluntary participations.