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 Mycobacterium abscessus (Mab) in infected human macrophages, with functional or pharmacologically inhibited cystic fibrosis conductance regulator (CFTR). Here, we evaluated the in vitro 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.