Defective MyD88 and IRAK4 but not TLR-2 expression in HIV+ individuals with latent tuberculosis infection

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2018-10, Vol.110, p.213-221
• Main Authors: Devalraju, Kamakshi Prudhula, Neela, Venkata Sanjeev Kumar, Gaddam, Ramulu, Chaudhury, Arunabala, Van, Abhinav, Krovvidi, Siva Sai, Vankayalapati, Ramakrishna, Valluri, Vijaya Lakshmi
• Format: Article
• Language: English
• Subjects: Cell Line; Chemokine CCL2 - metabolism; Chemokine CXCL10 - metabolism; Cytokines; HIV; HIV Infections - metabolism; Human; Humans; Interleukin-1 Receptor-Associated Kinases - metabolism; Interleukin-1beta - metabolism; Latent Tuberculosis - metabolism; Lipopolysaccharide Receptors - metabolism; Monocytes; Mycobacterium tuberculosis - pathogenicity; Myeloid Differentiation Factor 88 - metabolism; Signal Transduction - physiology; TLR-2; Toll-Like Receptor 2 - metabolism; Tuberculosis
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2018.05.005

•Production of IL-1 β, TNF-a and IL-10 is independent of TLR2 expression on monocytes.•MyD88 and IRAK4, not NF-kB mediate production of IL-1β, MCP-1 and IP-10 by CD14+ cells in HIV infection.•We hypothesize that this defect could be a reason for activation of latent TB in HIV. HIV infection markedly increases the likelihood of latent tuberculosis infection progressing to active TB. Information on expression of TLR-2, myeloid differentiation factor (MyD88), IL-1R- associated kinase-4 (IRAK4) and nuclear factor kappa B (NF-kB) in HIV+LTBI+ and HIV+ patients with active TB disease is limited. We found significantly higher percentages of CD14+TLR2+ cells in PBMCs of HIV+LTBI+ patients compared to HIV−LTBI+ individuals. γ-irradiated Mtb was unable to induce MyD88, IRAK4 expression and IL-1β, MCP-1, IP-10 production in HIV+LTBI+ patients. Pleural fluids from HIV+TB+ patients had low IL-1β, MCP-1, IP-10 and high IL-10, TNF-α production. γ-irradiated Mtb stimulated CD14+ cells from HIV+TB+ patients had low IL-1β, MCP-1, IP-10 production and MyD88, IRAK4 and similar NF-kB expression compared to those from of HIV−TB+ patients. Our results suggest defective MyD88, IRAK4 but not NF-kB inhibit IL-1β, MCP-1 and IP-10 production by CD14+ cells of HIV+ individuals with LTBI and active TB disease in peripheral blood and at the site of disease.