Type III interferons are expressed in tuberculosis granulomas and promote an inflammatory phenotype in macrophages that differs from type I interferon

Autor: Priyanka Talukdar, Joshua T. Mattila, Beth A Fallert Junecko
Rok vydání: 2020
Předmět:
Zdroj: The Journal of Immunology. 204:149.15-149.15
ISSN: 1550-6606
0022-1767
Popis: Humans and non-human primates express four subtypes of type III interferons (IFNλs; IFNλ1-IFNλ4). Unlike type I interferons, which have been thoroughly investigated in tuberculosis (TB), the role of IFNλs and their effects on immunity in TB remain unknown, especially at the disease site. To better understand the role of IFNλs in TB, we examined IFNλ1 and IFNλ4 expression in cynomolgus macaques with TB and investigated the effects of IFNα/β, IFNλ1 and IFNλ4 signaling on macaque macrophages. Using IHC, we identified differential IFNλ1 and IFNλ4 expression in macrophages and neutrophils, including IFNλ4 localization in the nuclei of epithelioid macrophages. CD206+ macrophages and CD3+ cells in the airway expressed IFNλR while CD11c+ macrophages in the lymphocyte cuff of the granuloma expressed IFNλR. To measure IFNλ1 and IFNλ4’s effect on macrophage gene expression and compare these cytokines against IFNα/β, we used NanoString transcriptional profiling and Ingenuity Pathway Analysis (IPA) on cytokine-stimulated macrophages to identify differentially regulated pathways. We found that IFNα/β upregulated the greatest number of ISGs, followed by IFNλ1, whereas IFNλ4 stimulation had minimal effect on gene expression. Interestingly, pro-inflammatory genes including IL-1β, IL-8, TLR1, BATF were upregulated by IFNλ1 while IL-1β and TLR1 were downregulated by IFNα/β. To determine the effects of IFNλs on anti-mycobacterial macrophage responses, we used a reporter Mtb strain to determine how IFNλ1 and IFNλ4 effect the viability of Mycobacterium tuberculosis. Our data suggest that IFNλs have non-redundant properties with type 1 interferons that may promote macrophage activation, inflammation, and antibacterial activity in TB.
Databáze: OpenAIRE
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