Mycobacterial Antigen Driven Activation of CD14CD16 Monocytes Is a Predictor of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome


Tuberculosis and HIV majorly impact host immune responses, resulting in immune deregulation and inflammation-driven tissue damage. Initiation of anti-retroviral therapy in patients with HIV-TB co-infection may result in immune reconstitution inflammatory syndrome (TB-IRIS), a disorder associated with increased immunopathology due to unfettered inflammation after CD4+ T-cell reconstitution. Monocytes are critical to the innate immune system and play an important role in several inflammatory conditions associated with chronic infections. Immunopathogenesis of TB-IRIS has been linked to activation of the adaptive immune response against opportunistic infection, yet the role of monocytes is still unknown. Here we investigated associations between soluble markers of monocyte activation, differential activation of monocyte subsets and TB-IRIS prospectively in two geographically distinct HIV-TB co-infected patient cohorts. Prior to ART initiation, patients who developed IRIS displayed a biosignature of elevated soluble monocyte activation markers, which were closely related to the mycobacterial antigen load in sputum samples. Amongst monocyte subsets, we observed that pre-ART circulating CD14++CD16− cell frequency independently predicted TB-IRIS and expanded during IRIS events. This monocyte subset was tightly associated with systemic markers of inflammation, and was found to produce inflammatory cytokines. Identification of this monocyte subset and its link with inflammation may lead to conception of novel therapies reducing immunopathology in TB-IRIS.


Vyšlo v časopise: Mycobacterial Antigen Driven Activation of CD14CD16 Monocytes Is a Predictor of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004433
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004433

Souhrn

Tuberculosis and HIV majorly impact host immune responses, resulting in immune deregulation and inflammation-driven tissue damage. Initiation of anti-retroviral therapy in patients with HIV-TB co-infection may result in immune reconstitution inflammatory syndrome (TB-IRIS), a disorder associated with increased immunopathology due to unfettered inflammation after CD4+ T-cell reconstitution. Monocytes are critical to the innate immune system and play an important role in several inflammatory conditions associated with chronic infections. Immunopathogenesis of TB-IRIS has been linked to activation of the adaptive immune response against opportunistic infection, yet the role of monocytes is still unknown. Here we investigated associations between soluble markers of monocyte activation, differential activation of monocyte subsets and TB-IRIS prospectively in two geographically distinct HIV-TB co-infected patient cohorts. Prior to ART initiation, patients who developed IRIS displayed a biosignature of elevated soluble monocyte activation markers, which were closely related to the mycobacterial antigen load in sputum samples. Amongst monocyte subsets, we observed that pre-ART circulating CD14++CD16− cell frequency independently predicted TB-IRIS and expanded during IRIS events. This monocyte subset was tightly associated with systemic markers of inflammation, and was found to produce inflammatory cytokines. Identification of this monocyte subset and its link with inflammation may lead to conception of novel therapies reducing immunopathology in TB-IRIS.


Zdroje

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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