Changes in Mycobacterium tuberculosis-Specific Immunity With Influenza co-infection at Time of TB Diagnosis

• Published in: Frontiers in immunology Vol. 9; p. 3093
• Main Authors: Mendy, Joseph, Jarju, Sheikh, Heslop, Rhiannon, Bojang, Adama L., Kampmann, Beate, Sutherland, Jayne S.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 04.01.2019
• Subjects: Adult; Bacterial Load; Cohort Studies; Coinfection - blood; Coinfection - diagnosis; Coinfection - immunology; Coinfection - microbiology; cytokines; DNA, Bacterial - isolation & purification; Female; flow cytometry; Gambia; Humans; Immunology; influenza; Influenza A virus - genetics; Influenza A virus - immunology; Influenza A virus - isolation & purification; Influenza B virus - genetics; Influenza B virus - immunology; Influenza B virus - isolation & purification; Influenza, Human - blood; Influenza, Human - diagnosis; Influenza, Human - immunology; Influenza, Human - virology; Male; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - isolation & purification; RNA, Ribosomal, 16S - genetics; RNA, Viral - isolation & purification; Sputum - microbiology; tuberculosis; Tuberculosis, Pulmonary - blood; Tuberculosis, Pulmonary - diagnosis; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - microbiology; Young Adult; Gambia; influenza; cytokines; flow cytometry; bacterial load; tuberculosis
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.03093

Prior Influenza A viral (IAV) infection has been shown to increase susceptibility to tuberculosis (TB) and TB has also been shown to be a primary cause of death during pandemics, including the Spanish Influenza outbreak of 1918-1919. The majority of data has been obtained from mouse models, thus the aim of this study was to determine the impact of Flu co-infection on host immunity and disease severity in TB patients at diagnosis. Sputum from 282 patients with active TB were analyzed for presence of FluA/FluB RNA at presentation using multiplex PCR. Sputum RNA was also analyzed for (Mtb) load using S RNA amplification. Supernatants from digested sputum and Mtb antigen-stimulated whole blood were analyzed using multiplex cytokine arrays and PBMC were analyzed for cytokine production from CD4+ T, CD8+ T and Mucosal Associated Invariant T cells (MAITs). 12 (4.3%) of TB patients were found to have FluA or FluB viral RNA present in their sputum at the time of TB diagnosis. The TB/Flu co-infected patients had a significantly higher bacterial load compared to those with TB mono-infection ( = 0.0026). They had lower levels of IL17A in sputum ( = 0.0275) and higher MCP-1 (CCL2) levels in the blood following PPD stimulation ( = 0.0267). TB/Flu co-infected subjects had significantly higher IFN-γ+IL-17+CD4+ and IFN-γ+IL-17-CD8+ cells compared to TB mono-infected subjects. These data show that Flu co-infection at time of TB diagnosis is associated with a higher bacterial load and differential cellular and soluble profiles. These findings show for the first time the impact of TB/Flu co-infection in a human cohort and support the potential benefit of Flu vaccination in TB-endemic settings.