Early diagnosis and role of immunological memory in nontuberculous mycobacterial lung infections in patients with cystic fibrosis

• Grant number: 19/14134-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: January 06, 2020
• End date: January 05, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Marcos Tadeu Nolasco da Silva
• Grantee: Renan Marrichi Mauch
• Supervisor: Niels Høiby
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Copenhagen, Copenhagen, Denmark
• Associated to the scholarship: 18/10614-0 - Innate and adaptive immune response in the persistence of Pseudomonas aeruginosa lung biofilm infection in cystic fibrosis, BP.PD

Abstract

There is an urgent need to develop a method to be used to diagnose early and latent nontuberculous mycobacteria (NTM) infection in persons with cystic fibrosis (CF). The prevalence of Mycobacterium abscessus complex (MABSC) is increasing among Danish CF patients and the effect on lung function is devastating. Despite treatment, less than a third of patients with MABSC were able to clear the infection and one-fourth eventually underwent lung transplant or died. Delays in diagnosis are likely to occur, stressing the need for alternative diagnostic tests. Here, we aim to develop a cellular-based immune assay inspired from the successful tuberculosis (TB) interferon-gamma (IFN-³) release assay, which has improved outcomes of patients with TB, to diagnose early and latent NTM infection. In addition, we aim to investigate differences in the adaptive immune response (with a particular focus on immunological memory) against Mycobacterium avium complex (MAC) and MABSC between CF patients seen at the Rigshospitalet (Copenhagen, Denmark) and University of Campinas (CERFC - Campinas, Brazil) CF reference centers, using a flow cytometric immunophenotyping assay, as well as the possible role of the Bacille Calmette-Guérin (BCG) vaccination (routinely performed in Brazil but not in Denmark) in this context, which has not been investigated so far and may explain the contrasting frequencies of NTM between these two centers. This research project is part of the well established cooperation between CERFC's and Rigshospitalet's CF study groups. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MAUCH, RENAN MARRICHI; JENSEN, PETER OSTRUP; QVIST, TAVS; KOLPEN, METTE; MOSER, CLAUS; PRESSLER, TACJANA; DA SILVA, MARCOS TADEU NOLASCO; HOIBY, NIELS; COPENHAGEN STUDY GRP MYCOBACTERIAL INFECT CYST FIBROSIS. Adaptive Immune Response to Mycobacterium abscessus Complex (MABSC) in Cystic Fibrosis and the Implications of Cross-Reactivity. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 13-pg., 2022-04-20. (19/14134-5, 19/08598-9)