Expression of Intron-containing HIV-1 RNA Induces NLRP1 Inflammasome Activation in Myeloid Cells DOI Creative Commons

Sallieu Jalloh,

I A Hughes,

Hisashi Akiyama

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

Abstract Despite the success of antiretroviral therapy (ART) in suppressing plasma viremia people living with human immunodeficiency virus type-1 (HIV-1), persistent viral RNA expression tissue reservoirs is observed and can contribute to HIV-1-induced immunopathology comorbidities. Infection long-lived innate immune cells, such as tissue-resident macrophages microglia may production chronic inflammation. We recently reported that de-novo cytoplasmic HIV-1 intron-containing (icRNA) leads MDA5 MAVS-dependent sensing induction type I IFN responses, demonstrating HIV icRNA a pathogen-associated molecular pattern (PAMP). In this report, we show also induces NLRP1 inflammasome activation IL-1β secretion RLR- endosomal TLR-independent manner. both either replication-competent or single-cycle induced secretion, which was attenuated when prevented. While blocked by treatment caspase-1 inhibitors knockdown HIV- infected macrophages, overexpression significantly enhanced an HIV-icRNA-dependent Immunoprecipitation analysis revealed interaction icRNA, but not multiply-spliced RNA, NLRP1, suggesting sufficient trigger activation. Together, these findings reveal pathway de novo expressed myeloid cells.

Language: Английский

Comprehensive analysis of SARS‐CoV‐2 receptor proteins in human respiratory tissues identifies alveolar macrophages as potential virus entry site DOI Creative Commons
Konstantin Bräutigam, Stefan Reinhard, Martin Wartenberg

et al.

Histopathology, Journal Year: 2023, Volume and Issue: 82(6), P. 846 - 859

Published: Jan. 26, 2023

COVID-19 has had enormous consequences on global health-care and resulted in millions of fatalities. The exact mechanism site SARS-CoV-2 entry into the body remains insufficiently understood. Recently, novel virus receptors were identified, alveolar macrophages suggested as a potential viral cell type vector for intra-alveolar transmission. Here, we investigated protein expression 10 well-known molecules along sites humans using immunohistochemistry.Samples different anatomical from up to 93 patients incorporated tissue microarrays. Protein ACE2, TMPRSS2, furin, CD147, C-type lectin (CD169, CD209, CD299), neuropilin-1, ASGR1 KREMEN1 analysed. In lung tissues, at least one three or was expressed majority cases. Moreover, all found be macrophages, co-localisation with N-protein demonstrated dual immunohistochemistry autopsy. While CD169 CD209 showed consistent sinonasal, conjunctival bronchiolar neuropilin-1 mostly absent, suggesting minor relevance these two specific sites.Our results extend recent discoveries indicating role sites. they support notion being SARS-CoV-2.

Language: Английский

Citations

3
SARS-CoV2 infection in whole lung primarily targets macrophages that display subset-specific responses DOI Creative Commons
Thien‐Phong Vu Manh,

Carla Gouin,

Julien De Wolf

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 14, 2024

Abstract Deciphering the initial steps of SARS-CoV-2 infection, that influence COVID-19 outcomes, is challenging because animal models do not always reproduce human biological processes and in vitro systems recapitulate histoarchitecture cellular composition respiratory tissues. To address this, we developed an innovative ex vivo model whole lung infection with SARS-CoV-2, leveraging a transplantation technique. Through single-cell RNA-seq, identified alveolar monocyte-derived macrophages (AMs MoMacs) were targets virus. Exposure isolated AMs, MoMacs, classical monocytes non-classical (ncMos) to variants revealed while all subsets responded, MoMacs produced higher levels inflammatory cytokines than ncMos contributed least. A Wuhan lineage appeared be more potent D614G virus, in dose-dependent manner. Amidst ambiguity literature regarding cell target, our study reveals AMs are dominant primary entry points for suggests their responses may conduct subsequent injury, depending on abundance, viral strain dose. Interfering virus interaction should considered prophylactic strategies.

Language: Английский

Citations

0
Immunology of SARS-CoV-2 infection DOI
Aida G. Gabdoulkhakova,

Rimma N. Mingaleeva,

Albina M. Romozanova

et al.

Биохимия, Journal Year: 2024, Volume and Issue: 89(1), P. 74 - 93

Published: July 31, 2024

According to WHO data, about 800 million of the world population had contracted a coronavirus infection caused by SARS-CoV-2 mid-2023. The properties this virus allowed it circulate in human for long time, evolving defense mechanisms against host immune system. severity disease depends largely on degree activation systemic response, including overstimulation macrophages and monocytes, cytokine production, triggering adaptive T- B-cell responses while evading from system action. In review we discussed triggered response entry into cell malfunctions leading development severe disease.

Language: Английский

Citations

0
Kabasura Kudineer Choornam, a medicinal polyherbal formulation, modulates human macrophage polarization and phagocytic function DOI Open Access
Asli Korkmaz, Duygu Unuvar Purcu, Sinem Gunalp

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

Abstract Background Kabasura kudineer choornam ( KKC ) is a polyherbal formulation with 15 ingredients. It has been shown to have anti-inflammatory and anti-microbial properties demonstrate efficacy in managing the symptoms of H1N1 swine flu COVID-19. However, its mechanism action not fully comprehended. Purpose Herein, we examined effect on polarization function primary human macrophages. Methods Human monocyte-derived macrophages (M0 macrophages) pre-treated extract were polarized into M1, M2a, or M2c subtypes. The expression M1/M2 markers was analyzed by qPCR, flow cytometry, ELISA, phagocytosis capacity cytometry. Results Our data show that treatment increased M1 IDO1, IL-1β, IL-12a(p35), TNF both unpolarized at mRNA level. it decreased secretion IL-12 (p70) M0, IL-10 M0 M2a macrophages, while after treatment. Interestingly, all -treated macrophage phenotypes displayed downregulation surface CD64, CD206, CD209, CD163, which also play role phagocytosis. In accordance this result, phagocytic Conclusion conclusion, modulates inflammatory response could be potential supplement for infectious diseases.

Language: Английский

Citations

0
Expression of Intron-containing HIV-1 RNA Induces NLRP1 Inflammasome Activation in Myeloid Cells DOI Creative Commons

Sallieu Jalloh,

I A Hughes,

Hisashi Akiyama

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

Abstract Despite the success of antiretroviral therapy (ART) in suppressing plasma viremia people living with human immunodeficiency virus type-1 (HIV-1), persistent viral RNA expression tissue reservoirs is observed and can contribute to HIV-1-induced immunopathology comorbidities. Infection long-lived innate immune cells, such as tissue-resident macrophages microglia may production chronic inflammation. We recently reported that de-novo cytoplasmic HIV-1 intron-containing (icRNA) leads MDA5 MAVS-dependent sensing induction type I IFN responses, demonstrating HIV icRNA a pathogen-associated molecular pattern (PAMP). In this report, we show also induces NLRP1 inflammasome activation IL-1β secretion RLR- endosomal TLR-independent manner. both either replication-competent or single-cycle induced secretion, which was attenuated when prevented. While blocked by treatment caspase-1 inhibitors knockdown HIV- infected macrophages, overexpression significantly enhanced an HIV-icRNA-dependent Immunoprecipitation analysis revealed interaction icRNA, but not multiply-spliced RNA, NLRP1, suggesting sufficient trigger activation. Together, these findings reveal pathway de novo expressed myeloid cells.

Language: Английский

Citations

0