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

Eur J Immunol. 2023 Dec 31:e2350666. doi: 10.1002/eji.202350666. Online ahead of print.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.PMID:38161237 | DOI:10.1002/eji.202350666
Source: European Journal of Immunology - Category: Allergy & Immunology Authors: Source Type: research