MAC attack: MSCs and macrophages join forces against chronic lung infection

Mesenchymal stromal cells (MSCs) possess several characteristics that make them attractive as a potential adjunct therapy for acute and chronic infectious diseases. MSCs are well known for their impressive immunomodulatory,1 2 pro-repair effects1 3 and clinical safety profile,4 5 however, the efficacy of MSCs in controlling bacterial infections, at least directly, remains unclear.6

Mycobacterium avium complex pulmonary disease (MAC-PD) is a chronic condition driven by multi-drug resistant bacteria for which there are no robust efficacious treatment strategies.

MAC-PD is associated with high levels of morbidity, and long regimens of antimicrobial drugs, meaning there is an unmet need for novel therapeutics that can effectively target, modulate and re-educate the weakened immune system to effectively clear this bacterial infection. MAC infection predominantly affects macrophage and dendritic cell populations in the lung. Macrophages can be directly activated through MAC infection or by Th1 cells induced by antigen presenting cells. MAC can resist host defence mechanisms and persist in macrophages, where they act as a replication niche to support MAC dispersal.7 Thus, macrophages play a key role in MAC-disease pathogenesis.

Recently, interaction and communication between live or apoptotic MSCs and macrophages has been identified as one of the major mechanisms of action associated with MSC therapeutic efficacy.8–13 Thus, MSC-macrophage education may play a role in shaping functional macrophage bacterial clearance and disease progression.

A single study has …

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