Phosphatidylserine liposomes for Mycobacterium abscessus infections management in people with cystic fibrosis non-eligible for CFTR modulators

We previously demonstrated that phosphatidylserine liposomes (PS-L) reduce inflammation and enhance intracellular killing of <i>Mycobacterium abscessus</i> (Mab) in infected human macrophages, with functional or pharmacologically inhibited cystic fibrosis conductance regulator (CFTR). Here, we evaluated the <i>in vitro</i> therapeutic potential of PS-L in macrophages from people with cystic fibrosis (pwCF), either under therapeutic regimen or not with CFTR modulator therapy Elexacaftor/Tezacaftor/Ivacaftor (ETI). Results show that PS-L exerted an anti-inflammatory effect in Mab infected macrophages, reducing TNF-α and IL-1β production and inducing IL-10 release at early and late time points, respectively. In addition, PS-L significantly increased antimycobacterial activity in macrophages from pwCF either undergoing or not ETI regimen. Importantly, in ETI-ineligible pwCF, PS-L alone still was capable to enhance a significant antimycobacterial response. Finally, PS-L combined with amikacin further enhanced intracellular bacterial clearance compared to single treatments. Altogether, these findings support PS-L as a promising host-directed therapy against Mab infection, particularly for pwCF who cannot benefit from ETI.