Inflammation and immunomodulation in mycobacterial infection
Research type
Research Study
Full title
Investigating inflammation and immunomodulation in mycobacterial infection
IRAS ID
278747
Contact name
Cecilia O'Kane
Contact email
Sponsor organisation
Queen's University Belfast
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
The prevalence of non-tuberculous mycobacterial (NTM) pulmonary disease has increased rapidly over the past decade in Europe and the United States. NTM pulmonary disease (NTM-PD) occurs primarily in patients with pre-existing structural lung disease (such as cystic fibrosis, bronchiectasis and COPD) and causes further progressive inflammatory lung damage. There is also an association with T-cell immunodeficiency, with growing patient populations with primary immunodeficiency or using anti-TNF agents partly attributable to the rise in case numbers. However, not all pre-disposing factors to NTM-PD are known and cases are being described in healthy individuals.
NTM are intracellular bacteria and have developed strategies to enter and subvert the immune cells (macrophages) that normally clear them in humans. In susceptible patients, they form a protected replicative niche inside macrophages from where they escape to cause infection in neighbouring cells. The patient’s immune response to this process is characterized by excessive inflammation which damages the normal tissue structures in the lungs.
Isolates from the Mycobacterium avium complex (MAC) are the commonest cause of NTM pulmonary infections outside of the cystic fibrosis population. MAC are resistant to many antibiotics and typically require a 15-18 month course of combination antibiotics which are poorly tolerated and only successful in 60% of cases. In addition, these therapies do not target the dysregulated immune response, meaning that pulmonary tissue destruction continues during the protracted course of antibiotics.
In light of the rising incidence of NTM-PD, its severity on patient quality-of-life and the deficiency of current interventions, there is an urgent need to develop more efficacious and better tolerated therapies. We want to investigate and understand the immune response to NTM infection and test new strategies in the laboratory to assist bacterial clearance and reduce the lung damage caused by inflammation. Our ultimate aim is to better understand patient susceptibility to NTM and improve patient outcomes for these difficult infections.
REC name
London - Bromley Research Ethics Committee
REC reference
21/LO/0109
Date of REC Opinion
25 Feb 2021
REC opinion
Further Information Favourable Opinion