Neutrophil extracellular trap formation and gene programs distinguish TST/IGRA sensitization outcomes among < i > Mycobacterium tuberculosis < /i > exposed persons living with HIV

by Elouise E. Kroon, Wilian Correa-Macedo, Rachel Evans, Allison Seeger, Lize Engelbrecht, Jurgen A. Kriel, Ben Loos, Naomi Okugbeni, Marianna Orlova, Pauline Cassart, Craig J. Kinnear, Gerard C. Tromp, Marlo M öller, Robert J. Wilkinson, Anna K. Coussens, Erwin Schurr, Eileen G. Hoal

Persons living with HIV (PLWH) have an increased risk for tuberculosis (TB). After prolonged and repeated exposure, some PLWH never develop TB and show no evidence of immune sensitization toMycobacterium tuberculosis (Mtb) as defined by persistently negative tuberculin skin tests (TST) and interferon gamma release assays (IGRA). This group has been identified and defined as HIV+ persistently TB, tuberculin and IGRA negative (HITTIN). To investigate potential innate mechanisms unique to individuals with the HITTIN phenotype we compared their neutrophilMtb infection response to that of PLWH, with no TB history, but who test persistently IGRA positive, and tuberculin positive (HIT). Neutrophil samples from 17 HITTIN (PMNHITTIN) and 11 HIT (PMNHIT) were isolated and infected withMtb H37Rv for 1h and 6h. RNA was extracted and used for RNAseq analysis. Since there was no significant differential transcriptional response at 1h between infected PMNHITTIN and PMNHIT, we focused on the 6h timepoint. When compared to uninfected PMN, PMNHITTIN displayed 3106 significantly upregulated and 3548 significantly downregulated differentially expressed genes (DEGs) (absolute cutoff of a log2FC of 0.2, FDR

Source: PLoS Genetics - August 24, 2023 Category: Genetics & Stem Cells Authors: Elouise E. Kroon Source Type: research