MiR-144-3p is associated with pathological inflammation in patients infected with Mycobacteroides abscessus

Infection with rapidly growing nontuberculous mycobacteria is emerging as a global health issue; however, key host factors remain elusive. Here, we investigated the characteristic immune profiles of peripheral blood mononuclear cells (PBMCs) from patients infected with Mycobacteroides abscessus subsp. abscessus (Mabc) and M. abscessus subsp. massiliense (Mmass). Using an integrated analysis of global mRNA and microRNA expression profiles, we found that several inflammatory cytokines/chemokines [interleukin (IL)-1β, IL-6, C-X-C motif chemokine ligand 2, and C-C motif chemokine ligand 2] and miR-144-3p were significantly upregulated in PBMCs from patients compared with those from healthy controls (HCs). Notably, there was a strong correlation between the expression levels of miR-144-3p and proinflammatory cytokines/chemokines. Similarly, upregulated expression of miR-144-3p and proinflammatory cytokines/chemokines was found in macrophages and lungs from mice after infection with Mabc and Mmass. We showed that the expression of negative regulators of inflammation (SARM1 and TNIP3) was significantly downregulated in PBMCs from the patients, although they were not putative targets of miR-144-3p. Furthermore, overexpression of miR-144-3p led to a marked increase in proinflammatory cytokines/chemokines and promoted bacterial growth in macrophages. Together, our results highlight the importance of miR-144-3p linking to pathological inflammation during M. abscessus infection.
Nontuberculous mycobacteria: Regulatory and signalling molecules that promote inflammation A small RNA molecule which controls the expression of genes, and cell signaling molecules called cytokines are associated with the damaging inflammation caused by nontuberculous mycobacteria (NTM). NTM infections, which can affect most organs of the body, and are often resistant to most available drugs, are emerging as a serious global health concern. Patients with suppressed immunity are at particular risk. Increased production of a specific microRNA and of a variety of cytokines during NTM infection has been demonstrated by Hyeon Ji Kim and colleagues at Chungnam National University, Daejeon, and co-workers from other institutions in South Korea. Their findings come from comparing peripheral blood mononuclear cells in patients with Mycobacteroides abscessus lung infections with those from healthy controls. The researchers found similar increased microRNA and cytokine production in the lungs of infected mice.