Innate and adaptive immune response in the persistence of Pseudomonas aeruginosa lung biofilm infection in cystic fibrosis

• Grant number: 18/10614-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2019
• End date: December 31, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Marcos Tadeu Nolasco da Silva
• Grantee: Renan Marrichi Mauch
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 19/14134-5 - Early diagnosis and role of immunological memory in nontuberculous mycobacterial lung infections in patients with cystic fibrosis, BE.EP.PD

Abstract

Pulmonary disease is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). The remarkable mucus accumulation in the airways leads to chronic infections caused by a series of pathogens, with Pseudomonas aeruginosa being the predominant pathogen, mainly due to the adaptation mechanisms of this bacterium to the stress conditions of the CF airways, including biofilm formation. This infection is accompanied by an intense inflammatory response, mainly IgG-mediated, which does not clear infection. This may be due to impairment of immune memory formation against the pathogen despite repeated exposure to its antigens. Other emerging pathogens have been shown to play a significant role in the lung impairment, including non-tuberculous mycobacteria (NTM), frequently isolated from patients in some European reference centers (particularly in Denmark). However, the NTM prevalence in our center was shown to be low, which may be a consequence of the routinely applied BCG vaccine against tuberculosis. Here we propose to establish a profile of the innate and adaptive immune response in different groups of CF patients classified according to their P. aeruginosa lung colonization/infection status - never colonized, free of infection, intermittent colonization and chronic infection. This will help to better understand the foundations of immune flaws in CF and possibly the mechanisms P. aeruginosa uses to evade immune responses, and may also serve as a basis for other chronic infection models. Such knowledge will potentially provide support for the study of immunotherapeutic approaches for P. aeruginosa infection, aiming at functional preservation and improvement of survival. We also intend to evaluate and compare the innate and adaptive immune response against NTM in Brazilian and Danish patients and to investigate whether BCG vaccine has a role on the low NTM prevalence in our reference center. This project is part of the continuation of international cooperation already established between the FC study groups of Unicamp and the Department of Clinical Microbiology, Copenhagen University Hospital (Rigshospitalet), University of Copenhagen, Denmark.

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 M.; HENTSCHEL, JULIA; AANAES, KASPER; BARUCHA, ANTON; NOLASCO DA SILVA, MARCOS T.; LEVY, CARLOS E.; HOIBY, NIELS; MAINZ, JOCHEN G.. Antibody response against Pseudomonas aeruginosa and its relationship with immune mediators in the upper and lower airways of cystic fibrosis patients. PEDIATRIC PULMONOLOGY, v. 55, n. 4, FEB 2020. (18/10614-0)

MAUCH, RENAN M.; MANSINHO, ANDREA A. S.; ROCHA, PRISCILLA M. O.; ZACCARIOTTO, TANIA R.; LEVY, CARLOS E.; NOLASCO DA SILVA, MARCOS T.. Nontuberculous mycobacterial infections in a Brazilian pediatric population: a seven-year survey. PATHOGENS AND GLOBAL HEALTH, v. 114, n. 2, FEB 2020. (18/10614-0)

MAUCH, RENAN M.; ALVES, PAULO CESAR M.; LEVY, CARLOS E.; RIBEIRO, JOSE D.; RIBEIRO, ANTONIO F.; HOIBY, NIELS; NOLASCO DA SILVA, MARCOS T.. Lymphocyte responses to Mycobacterium tuberculosis and Mycobacterium bovis are similar between BCG-vaccinated patients with cystic fibrosis and healthy controls. Journal of Cystic Fibrosis, v. 19, n. 4, p. 575-579, JUL 2020. (19/08598-9, 18/10614-0)