IL-10 and Type I IFN Restrict MHC-II Trafficking in Mtb-Infected Macrophages

10 Jul 20264 min read0 viewsVerified Feed

GIST (Key Takeaways)

Recognition of infected macrophages by CD4+ T cells is essential to immune protection against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). However, not all infected macrophage subsets successfully elicit T cell activation.
We recently discovered that M2-like macrophages fail to efficiently activate memory CD4+ T cells when infected with Mtb, yet successfully elicit T cell activation when loaded with peptides, g-irradiated bacteria, or Mtb whole cell lysate. Since the mechanisms underlying CD4+ T cell evasion by infected M2 but not M1-like macrophages remain underexplored, we sought to determine the genes and pathways unique to Mtb infection of M2-like cells, including alveolar macrophages.
RNA sequencing of human macrophages infected with virulent Mtb identified enrichment of IL-10 and type I interferon (IFN) signaling genes, including IL10RA and HERC5, respectively, in infected M2-like monocyte-derived and alveolar macrophages. However, genes involved in MHC-II trafficking, such as AP1M2, were higher in infected M1-like macrophages.