Neutrophil‐plasmacytoid dendritic cell interaction leads to production of type I IFN in response to Mycobacterium tuberculosis

Abstract

AbstractMycobacterium tuberculosis (Mtb) can cause a latent infection that sometimes progresses to clinically active tuberculosis (TB). Type I interferons (IFN‐I) have been implicated in initiating the progression from latency to active TB, in part because IFN‐I stimulated genes are the earliest genes to be upregulated in patients as they advance to active TB. Plasmacytoid dendritic cells (pDCs) are major producers of IFN‐I during viral infections and in response to autoimmune‐induced neutrophil extracellular traps. pDCs have also been suggested to be the major producers of IFN‐I during Mtb infection of mice and nonhuman primates, but direct evidence has been lacking. Here, we found that Mtb did not stimulate isolated human pDCs to produce IFN‐I, but human neutrophils infected with Mtb‐activated co‐cultured pDCs to do so. Mtb‐infected neutrophils produced neutrophil extracellular traps, whose exposed DNA is a well‐known mechanism to activate pDCs to secrete IFN‐I. We conclude that pDCs contribute to the IFN‐I response during Mtb infection by interacting with infected neutrophils which may then promote Mtb pathogenesis.