TY - JOUR
T1 - Chronic HIV infection induces transcriptional and functional reprogramming of innate immune cells
AU - van der Heijden, Wouter A.
AU - Van de Wijer, Lisa
AU - Keramati, Farid
AU - Trypsteen, Wim
AU - Rutsaert, Sofie
AU - ter Horst, Rob
AU - Jaeger, Martin
AU - Koenen, Hans J.P.M.
AU - Stunnenberg, Hendrik G.
AU - Joosten, Irma
AU - Verweij, Paul E.
AU - van Lunzen, Jan
AU - Dinarello, Charles A.
AU - Joosten, Leo A.B.
AU - Vandekerckhove, Linos
AU - Netea, Mihai G.
AU - van der Ven, André J.A.M.
AU - de Mast, Quirijn
N1 - Publisher Copyright:
© 2021, van der Heijden et al.
PY - 2021/4/8
Y1 - 2021/4/8
N2 - Chronic inflammation and immune dysfunction play a key role in the development of non-AIDS- related comorbidities. The aim of our study was to characterize the functional phenotype of immune cells in people living with HIV (PLHIV). We enrolled a cross-sectional cohort study of PLHIV on stable antiretroviral therapy and healthy controls. We assessed ex vivo cytokine production capacity and transcriptomics of monocytes and T cells upon bacterial, fungal, and viral stimulation. PLHIV exhibited an exacerbated proinflammatory profile in monocyte-derived cytokines, but not in lymphocyte-derived cytokines. Particularly, the production of the IL-1β to imiquimod, E. coli LPS, and Mycobacterium tuberculosis was increased, and this production correlated with plasma concentrations of high-sensitivity C-reactive protein and soluble CD14. This increase in monocyte responsiveness remained stable over time in subsequent blood sampling after more than 1 year. Transcriptome analyses confirmed priming of the monocyte IL-1β pathway, consistent with a monocyte-trained immunity phenotype. Increased plasma concentrations of β-glucan, a wellknown inducer of trained immunity, were associated with increased innate cytokine responses. Monocytes of PLHIV exhibited a sustained proinflammatory immune phenotype with priming of the IL-1β pathway. Training of the innate immune system in PLHIV likely plays a role in long-term HIV complications and provides a promising therapeutic target for inflammation-related comorbidities.
AB - Chronic inflammation and immune dysfunction play a key role in the development of non-AIDS- related comorbidities. The aim of our study was to characterize the functional phenotype of immune cells in people living with HIV (PLHIV). We enrolled a cross-sectional cohort study of PLHIV on stable antiretroviral therapy and healthy controls. We assessed ex vivo cytokine production capacity and transcriptomics of monocytes and T cells upon bacterial, fungal, and viral stimulation. PLHIV exhibited an exacerbated proinflammatory profile in monocyte-derived cytokines, but not in lymphocyte-derived cytokines. Particularly, the production of the IL-1β to imiquimod, E. coli LPS, and Mycobacterium tuberculosis was increased, and this production correlated with plasma concentrations of high-sensitivity C-reactive protein and soluble CD14. This increase in monocyte responsiveness remained stable over time in subsequent blood sampling after more than 1 year. Transcriptome analyses confirmed priming of the monocyte IL-1β pathway, consistent with a monocyte-trained immunity phenotype. Increased plasma concentrations of β-glucan, a wellknown inducer of trained immunity, were associated with increased innate cytokine responses. Monocytes of PLHIV exhibited a sustained proinflammatory immune phenotype with priming of the IL-1β pathway. Training of the innate immune system in PLHIV likely plays a role in long-term HIV complications and provides a promising therapeutic target for inflammation-related comorbidities.
UR - https://www.scopus.com/pages/publications/85104159877
U2 - 10.1172/jci.insight.145928
DO - 10.1172/jci.insight.145928
M3 - Article
C2 - 33630761
AN - SCOPUS:85104159877
SN - 2379-3708
VL - 6
JO - JCI Insight
JF - JCI Insight
IS - 7
M1 - e145928
ER -