Mycobacterium abscessus ESX-3 plays an important role in host inflammatory and pathological responses during infection

Abstract Mycobacterial ESX systems are often related to pathogenesis during infection. However, little is known about the function of ESX systems of Mycobacterium abscessus (Mab). This study focuses on the Mab ESX-3 cluster, which contains major genes such as esxH (Rv0288, low molecular weight protein antigen 7; CFP-7) and esxG (Rv0287, ESAT-6 like protein). An esx-3 (MAB 2224c-2234c)-deletional mutant of Mab (Δ esx ) was constructed and used to infect murine and human macrophages. We then investigated whether Mab Δ esx modulated innate host immune responses in macrophages. Mab Δ esx infection resulted in less pathological and inflammatory responses. Additionally, Δ esx resulted in significantly decreased activation of inflammatory signaling and cytokine production in macrophages compared to WT. Moreover, recombinant EsxG·EsxH (rEsxGH) proteins encoded by the ESX-3 region showed synergistic enhancement of inflammatory cytokine generation in macrophages infected with Δ esx . Taken together, our data suggest that Mab ESX-3 plays an important role in inflammatory and pathological responses during Mab infection.