Type I interferon induced by TLR2-TLR4-MyD88-TRIF-IRF3 controls Mycobacterium abscessus subsp. abscessus persistence in murine macrophages via nitric oxide.

In this study, we analyzed the IFNβ expression of murine macrophages infected with a MAB rough colony strain (MAB-R) isolated from a patient with progressive CF and compared it to macrophages infected with the MAB smooth colony type reference strain (MAB-S). We found that MAB-R infected macrophages expressed significantly more IFNβ mRNA and protein than MAB-S infected macrophages. Higher IFNβ induction by MAB-R was associated with higher TNF expression and intracellular killing while low IFNβ induction was associated with lower TNF expression and persistence of MAB-S. IFNβ induction was independent of the intracellular cGAS-STING recognition pathway. MAB appeared to be recognized extracellularly and induced IFNβ expression via TLR2-TLR4-MyD88-TRIF-IRF3 dependent pathways. By using macrophages lacking the IFN-I receptor we demonstrate that MAB induced IFN-I response essentially contributed to restricting MAB-R and MAB-S infections by activating macrophage Nos2 expression and nitric oxide production. Thus IFN-I seem to influence the intrinsic ability of macrophages to control MAB infections. As MAB persists over long time periods in susceptible patients, our findings suggest that virulence of MAB strains is promoted by an insufficient IFN-I response of the host. PMID: 31178418 [PubMed - as supplied by publisher]
Source: International Journal of Medical Microbiology - Category: Microbiology Authors: Tags: Int J Med Microbiol Source Type: research