Investigating the antimicrobial efficacy of MSCs as a potential novel therapy for Mycobacterium avium pulmonary infection

Abstract

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) has rapidly increased in global prevalence over the last two decades. NTM-PD occurs mainly in patients with pre-existing structural lung disease and current treatment strategies are often ineffective and poorly tolerated. Outside of the cystic fibrosis population, the most common NTM isolates are from Mycobacterium avium complex (MAC). Mesenchymal stromal cells (MSCs) have potent antimicrobial and immunomodulatory properties including direct microbial killing and enhancement of phagocytic function. Their effect on MAC species is unknown. Human MSCs were infected with M. avium at a multiplicity of infection (MOI) of 2. Human monocyte-derived macrophages (MDMs) were also infected with a clinical isolate of M. avium at MOI of 2. After 4 h, MSCs were added at a ratio of 1 MSC:3 MDMs. After 24 and 74 h, colony counts were performed on supernatants and cell lysates. MSCs reduced total bacterial counts of M. avium by 24 % at 24 h (from 295×103/ml to 225×103/ml, P<0.05) and 40 % at 72 h (from 403×103/ml to 243×103/ml, P<0.05). MSCs reduced total bacterial counts of M. avium in infected MDMs by >40 % (from 381×103/ml to 209×103/ml, P<0.05) after 24 h and >70 % after 72 h (from 1050×103/ml to 314×103/ml, P<0.05). MSCs have modest direct antimicrobial effect against MAC, but potently enhance their killing by macrophages. Mechanistic studies are required to understand the mechanisms of the antimicrobial effect, with the aim of exploiting these therapeutically in pulmonary MAC disease.