HIV Interferes with Mycobacterium tuberculosis Antigen Presentation in Human Dendritic Cells
| Autor: | Robert Blomgran, Olle Stendahl, Susmita K. Singh, Marie Larsson, Cecilia S. Lindestam Arlehamn, Alessandro Sette, Anna-Maria Andersson, Rada Ellegård |
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| Rok vydání: | 2016 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine Antigen presentation HIV Infections chemical and pharmacologic phenomena Biology Lymphocyte Activation Major histocompatibility complex Pathology and Forensic Medicine 03 medical and health sciences Immune system Antigen Antigens CD Humans Tuberculosis Antigen Presentation Antigens Bacterial CD40 Coinfection Antigen processing Histocompatibility Antigens Class II Dendritic Cells Mycobacterium tuberculosis Dendritic cell Acquired immune system Virology Coculture Techniques 030104 developmental biology Gene Expression Regulation Immunology HIV-1 biology.protein Cytokines |
| Zdroj: | The American Journal of Pathology. 186:3083-3093 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2016.08.003 |
| Popis: | HIV coinfection is the most prominent risk factor for progression of Mycobacterium tuberculosis (Mtb) infection into active tuberculosis (TB) disease. The mechanisms behind the increased transition from latent to active TB in coinfected individuals have not been well elucidated at the cellular level. We hypothesized that HIV infection contributes to Mtb pathogenesis by interfering with the dendritic cell (DC)–mediated immune control. Mtb-antigen processing and presentation are key events in the immune response against TB. Human immature DCs coinfected with HIV/Mtb had decreased expression of human leukocyte antigen antigen D related and the costimulatory molecules CD40, CD80, and CD86. In addition, Mtb-infected DCs triggered a significant release of the proinflammatory cytokines IL-6, IL-1β, and tumor necrosis factor-α, whereas coinfected DCs did not. To assess the DC antigen presentation capacity, we measured interferon-γ from co-cultures of DCs and autologous Mtb antigen-specific CD4 + T cells. Interferon-γ release was significantly reduced when purified protein derivative– and Ag85B-specific CD4 + T cells had been activated with coinfected DCs compared to Mtb-infected DCs, and this effect was attributed to Mtb antigen processing rather than peptide–major histocompatibility complex class II loading. Evaluating autophagy as a measure of vesicular processing and maturation further revealed that HIV efficiently blocks initiation of this pathway during coinfection. Overall, our results demonstrate that HIV impairs Mtb antigen presentation in DCs, thereby suppressing an important cell linking innate and adaptive immune response in TB. |
| Databáze: | OpenAIRE |
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