HIV-1 induces NALP3-inflammasome expression and interleukin-1β secretion in dendritic cells from healthy individuals but not from HIV-positive patients

Pontillo, Alessandra; Silva, Lais T.; Oshiro, Telma Miyuki; Finazzo, C.; Crovella, Sérgio; Duarte, Alberto J. S.

doi:10.1097/qad.0b013e32834d697f

Cited by 67 publications

(66 citation statements)

References 16 publications

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“…The secretion of the proinflammatory factor IL-1b requires instigation of the inflammasome by an activator. We found that F-HIV but not C-HIV induced the secretion of IL-1b in iDCs and PKR, recently identified as activator of the inflammasome, was upregulated by F-HIV, indicating that it could be the activator of the NALP3 inflammasome (45,46).…”

Section: Discussionmentioning

confidence: 88%

Complement Opsonization of HIV-1 Results in Decreased Antiviral and Inflammatory Responses in Immature Dendritic Cells via CR3

Ellegård

Crisci

Burgener

et al. 2014

The Journal of Immunology

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Immature dendritic cells (iDCs) in genital and rectal mucosa may be one of the first cells to come into contact with HIV-1 during sexual transmission of virus. HIV-1 activates the host complement system, which results in opsonization of virus by inactivated complement fragments, for example, iC3b. We investigated antiviral and inflammatory responses induced in human iDCs after exposure to free HIV-1 (F-HIV), complement-opsonized HIV-1 (C-HIV), and complement and Ab–opsonized HIV-1 (CI-HIV). F-HIV gave rise to a significantly higher expression of antiviral factors such as IFN-β, myxovirus resistance protein A, and IFN-stimulated genes, compared with C-HIV and CI-HIV. Additionally, F-HIV induced inflammatory factors such as IL-1β, IL-6, and TNF-α, whereas these responses were weakened or absent after C-HIV or CI-HIV exposure. The responses induced by F-HIV were TLR8-dependent with subsequent activation of IFN regulatory factor 1, p38, ERK, PI3K, and NF-κB pathways, whereas these responses were not induced by C-HIV, which instead induced activation of IFN regulatory factor 3 and Lyn. This modulation of TLR8 signaling was mediated by complement receptor 3 and led to enhanced infection. The impact that viral hijacking of the complement system has on iDC function could be an important immune evasion mechanism used by HIV-1 to establish infection in the host.

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Section: Discussionmentioning

confidence: 88%

Complement Opsonization of HIV-1 Results in Decreased Antiviral and Inflammatory Responses in Immature Dendritic Cells via CR3

Ellegård

Crisci

Burgener

et al. 2014

The Journal of Immunology

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“…These findings suggest that NLRP3 can be activated by virus-encoded viroporins due to their ability to disrupt the cellular ion balance. In the context of human immunodeficiency virus (HIV) infection, NLRP3 inflammasome activation is observed during the early onset of the HIV disease and HIV infection has been shown to activate the NLRP3 inflammasome and IL-1b secretion in DCs from healthy individuals, but not in those from HIVpositive individuals [61]. In addition to the aforementioned viruses, several other RNA viruses have been reported to activate the NLRP3 inflammasome.…”

Section: Rna Virusesmentioning

confidence: 99%

Inflammasomes and its importance in viral infections

León-Juárez²,

et al. 2016

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A complex interplay between pathogen and host determines the immune response during viral infection. A set of cytosolic sensors are expressed by immune cells to detect viral infection. NOD-like receptors (NLRs) comprise a large family of intracellular pattern recognition receptors. Members of the NLR family assemble into large multiprotein complexes, termed inflammasomes, which induce downstream immune responses to specific pathogens, environmental stimuli, and host cell damage. Inflammasomes are composed of cytoplasmic sensor molecules such as NLRP3 or absent in melanoma 2 (AIM2), the adaptor protein ASC (apoptosis-associated speck-like protein containing caspase recruitment domain), and the effector protein procaspase-1. The inflammasome operates as a platform for caspase-1 activation, resulting in caspase-1-dependent proteolytic maturation and secretion of interleukin (IL)-1b and IL-18. This, in turn, activates the expression of other immune genes and facilitates lymphocyte recruitment to the site of primary infection, thereby controlling invading pathogens. Moreover, inflammasomes counter viral replication and remove infected immune cells through an inflammatory cell death, program termed as pyroptosis. As a countermeasure, viral pathogens have evolved virulence factors to antagonise inflammasome pathways. In this review, we discuss the role of inflammasomes in sensing viral infection as well as the evasion strategies that viruses have developed to evade inflammasome-dependent immune responses. This information summarises our understanding of host defence mechanisms against viruses and highlights research areas that can provide new approaches to interfere in the pathogenesis of viral diseases.

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“…It has bene reported that viral infection or viral RNA transfection can trigger NLRP3 inflammasome activation (15,17,60). However, none of the known components (NLRP3, ASC, and caspase-1) in the NLRP3 inflammasome has the ability to bind viral RNA.…”

Section: Ddx19a Is Identified As a Novel Component In Nlrp3 Inflammasomementioning

confidence: 99%

“…It has been demonstrated that viral infections can induce the NLRP3 inflammasome activation (10,17,(58)(59)(60). We then investigated whether the NLRP3-ASC-caspase-1 complex is formed in response to HP-PRRSV infection.…”

Section: Hp-prrsv Infection Induces Nlrp3-dependent Inflammasome Actimentioning

confidence: 99%

DDX19A Senses Viral RNA and Mediates NLRP3-Dependent Inflammasome Activation

Liu

et al. 2015

The Journal of Immunology

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The NLRP3 inflammasome plays a major role in innate immune responses by activating caspase-1, resulting in secretion of IL-1β and inflammatory pathologic responses. Viral RNA can induce NLRP3 inflammasome activation. However, none of the components of NLRP3 inflammasome has the ability to bind viral RNA. Therefore, it had been proposed that there might have been some unidentified cytosolic RNA sensors that could bind viral RNA and NLRP3 to initiate NLRP3 inflammasome activation. In this study, DDX19A, a member of the DEAD/H-box protein family, was identified as a novel component of NLRP3 inflammasome using arterivirus infection as a model. We found that DDX19A interacted with viral RNA and NLRP3. Knockdown of DDX19A expression efficiently inhibited procaspase-1 cleavage and IL-1β secretion in porcine reproductive and respiration syndrome virus (PRRSV)–infected or PRRSV RNA-stimulated primary porcine alveolar macrophages. Overall, DDX19A was identified as a novel cytosolic RNA sensor that bridged PRRSV RNA and NLRP3 to activate NLRP3 inflammasome.

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HIV-1 induces NALP3-inflammasome expression and interleukin-1β secretion in dendritic cells from healthy individuals but not from HIV-positive patients

Cited by 67 publications

References 16 publications

Complement Opsonization of HIV-1 Results in Decreased Antiviral and Inflammatory Responses in Immature Dendritic Cells via CR3

Complement Opsonization of HIV-1 Results in Decreased Antiviral and Inflammatory Responses in Immature Dendritic Cells via CR3

Inflammasomes and its importance in viral infections

DDX19A Senses Viral RNA and Mediates NLRP3-Dependent Inflammasome Activation

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