Chronic HIV Infection Increases Monocyte NLRP3 Inflammasome-Dependent IL-1α and IL-1β Release

Author:

Hoel Hedda12,Dahl Tuva Børresdatter1ORCID,Yang Kuan1ORCID,Skeie Linda Gail3ORCID,Michelsen Annika Elisabet1,Ueland Thor14ORCID,Damås Jan Kristian56,Dyrhol-Riise Anne Ma34,Fevang Børre147,Yndestad Arne1,Aukrust Pål147,Trøseid Marius147ORCID,Sandanger Øystein18

Affiliation:

1. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway

2. Department of Internal Medicine, Lovisenberg Diaconal Hospital, 0440 Oslo, Norway

3. Department of Infectious Diseases, Oslo University Hospital, Ullevål, 0450 Oslo, Norway

4. Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway

5. Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7034 Trondheim, Norway

6. Department of Infectious Diseases, St. Olavs Hospital, 7030 Trondheim, Norway

7. Section of Clinical Immunology and Infectious Diseases, Department of Rheumatology, Dermatology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway

8. Section of Dermatology, Department of Rheumatology, Dermatology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway

Abstract

Antiretroviral treatment (ART) has converted HIV from a lethal disease to a chronic condition, yet co-morbidities persist. Incomplete immune recovery and chronic immune activation, especially in the gut mucosa, contribute to these complications. Inflammasomes, multi-protein complexes activated by innate immune receptors, appear to play a role in these inflammatory responses. In particular, preliminary data indicate the involvement of IFI16 and NLRP3 inflammasomes in chronic HIV infection. This study explores inflammasome function in monocytes from people with HIV (PWH); 22 ART-treated with suppressed viremia and 17 untreated PWH were compared to 33 HIV-negative donors. Monocytes were primed with LPS and inflammasomes activated with ATP in vitro. IFI16 and NLRP3 mRNA expression were examined in a subset of donors. IFI16 and NLRP3 expression in unstimulated monocytes correlated negatively with CD4 T cell counts in untreated PWH. For IFI16, there was also a positive correlation with viral load. Monocytes from untreated PWH exhibit increased release of IL-1α, IL-1β, and TNF compared to treated PWH and HIV-negative donors. However, circulating monocytes in PWH are not pre-primed for inflammasome activation in vivo. The findings suggest a link between IFI16, NLRP3, and HIV progression, emphasizing their potential role in comorbidities such as cardiovascular disease. The study provides insights into inflammasome regulation in HIV pathogenesis and its implications for therapeutic interventions.

Funder

South-Eastern Norway Regional Health Authorities

Publisher

MDPI AG

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