Bacterial pneumonia remains a major global disease burden. Klebsiella pneumoniae is a common cause of Gram-negative pneumonia in both children and adults. In recent years, the spread of carbapenem-resistant K. pneumoniae (CRKP) strains, which cause ≥50% mortality, has made treatment more difficult. Moreover, K. pneumoniae is known to cause life-threatening lung infections in patients with diabetes and in alcohol consumer. In addition, Bugs that are resistant to carbapenem, a last-resort antibiotic used to treat resistant infections, are among the most dangerous to human health, according to World Health Organization. In extreme cases, multi-drug-resistance leaves no treatment options. Thus, the emergence of multidrug resistant K. pneumoniae strains necessitate the investigation of alternative therapeutic options.

One strategy would be to use cell-based therapies to enhance host defense mechanisms against invading pathogens. Recently, the use of bone marrow-derived mesenchymal stem cells has received much attention in the treatment of various inflammatory and infectious diseases including bacterial pneumonia. However, the role of lung stem/mesenchymal stem cells in infections caused by bacteria is largely unknown. Our recent studies using a purified murine Sca-1⁺ lung mesenchymal stem cells (Sca-1⁺ LMSCs) revealed the immunomodulatory and antibacterial properties of these cells in both in vitro cell culture and in vivo animal models. Sca-1⁺ LMSCs have the capacity to inhibit LPS-induced secretion of inflammatory cytokines by bone marrow-derived macrophages and neutrophils in vitro. In addition, Sca-1⁺ LMSCs inhibit the growth of K. pneumoniae more potently than neutrophils. Sca-1⁺ LMSCs also possess the intrinsic ability to phagocytize and kill K. pneumoniae and CRKP intracellularly. Moreover, pre-treatment with the autophagy inhibitor, 3-Methyladenonine, enhanced the replication of CRKP and suppressed the replication of K. pneumoniae in Sca1⁺ LMSCs. Intriguingly, administration of Sca1⁺ LMSCs, attenuated the infiltration of inflammatory cells (predominantly neutrophils) in BAL fluid and decreased bacterial burden in the lung, spleen, and liver of K. pneumoniae and CRKP infected mice.

Our study, show for the first time, the phagocytic capacity, intracellular bacterial killing ability, as well as protective role of LMSCs in pneumonia caused by K. pneumoniae and the multidrug-resistant CRKP. Future studies are needed to determine the mechanisms by which LMSCs exert their antibacterial functions in vivo.