HIV-antibody complexes enhance production of type I interferon by plasmacytoid dendritic cells

Veenhuis, Rebecca T.; Freeman, Zachary T.; Korleski, Jack; Cohen, Laura K.; Massaccesi, Guido; Tomasi, Alessandra; Boesch, Austin W.; Ackerman, Margaret E.; Margolick, Joseph B.; Blankson, Joel N.; Chattergoon, Michael A.; Cox, Andrea L.

doi:10.1172/jci95375

Cited by 17 publications

(24 citation statements)

References 71 publications

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“…Upon establishment of persistent viral infection, IFN-I is mainly produced by activated plasmacytoid dendritic cells (pDCs) and to a lesser extent by monocytes, macrophages, and conventional DCs (cDCs) by pathogen sensing [ 8 , 15 , 42 , 43 ]. A recent study has also shown that polyclonal Abs and Ab complexes found in HIV-1-infected subjects induced IFN-I production in pDCs [ 44 ]. As depicted in Figure 1 , sustained IFN-I expression drives dysregulation at the tissue as well as cellular level within the innate immune response.…”

Section: Impact Of Sustained Ifn-i Expression On the Innate Immunementioning

confidence: 99%

Sustained IFN-I Expression during Established Persistent Viral Infection: A “Bad Seed” for Protective Immunity

Dagenais-Lussier

Loucif

Murira

et al. 2017

Viruses

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Type I interferons (IFN-I) are one of the primary immune defenses against viruses. Similar to all other molecular mechanisms that are central to eliciting protective immune responses, IFN-I expression is subject to homeostatic controls that regulate cytokine levels upon clearing the infection. However, in the case of established persistent viral infection, sustained elevation of IFN-I expression bears deleterious effects to the host and is today considered as the major driver of inflammation and immunosuppression. In fact, numerous emerging studies place sustained IFN-I expression as a common nexus in the pathogenesis of multiple chronic diseases including persistent infections with the human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), as well as the rodent-borne lymphocytic choriomeningitis virus clone 13 (LCMV clone 13). In this review, we highlight recent studies illustrating the molecular dysregulation and resultant cellular dysfunction in both innate and adaptive immune responses driven by sustained IFN-I expression. Here, we place particular emphasis on the efficacy of IFN-I receptor (IFNR) blockade towards improving immune responses against viral infections given the emerging therapeutic approach of blocking IFNR using neutralizing antibodies (Abs) in chronically infected patients.

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Section: Impact Of Sustained Ifn-i Expression On the Innate Immunementioning

confidence: 99%

Sustained IFN-I Expression during Established Persistent Viral Infection: A “Bad Seed” for Protective Immunity

Dagenais-Lussier

Loucif

Murira

et al. 2017

Viruses

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“…Because the body is not able to fully clear HIV, the virus is able to create a state of chronic immune activation believed to underlie many of the secondary pathologies associated with HIV (HIV-associated neurocognitive disorder (HAND), atherosclerosis, insulin resistance, renal failure, osteoporosis, and hepatitis), and be a major cause of disease progression to AIDS [12,34]. Sustained IFNα production by pDCs is implicated in this progression, a state potentially exacerbated by the presence of HIV-specific antibodies [36]. Chronic translocation of bacteria and bacterial products into the circulation from the gut, termed the "leaky gut hypothesis", has also been suggested to contribute to these sustained responses [23].…”

Section: Immune Responses To Viral Infectionsmentioning

confidence: 99%

“…Proper regulation of humoral immunity is important in a number of viral infections, notably HIV-1, where it has been shown that the body has the potential to develop potent broadly neutralizing antibodies against HIV-1 [76]. Importantly, the development of these broadly neutralizing antibodies can be a double-edged sword, as anti-HIV-1 antibodies can also chronically activate pDCs and allow for sustained IFNα production even in the presence of viral suppression [36]. Studies of SLAMF5 signaling in this pathogenic immune response would be highly relevant to understanding the body's natural response to HIV-1.…”

Section: Slamf5 (Cd84)mentioning

confidence: 99%

“…Monoclonal antibodies activating SLAMF9, specifically on pDCs, would, in theory, augment pDC IFNα production and anti-viral responses [29]. While the approach may be beneficial during acute viral infections, an opposite approach may be useful in chronic HIV infection, where constitutive pDC activation is evident and pathogenic [36].…”

Section: Potential For Targeting Slam Family Of Receptors In Hiv and mentioning

confidence: 99%

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SLAM Family Receptor Signaling in Viral Infections: HIV and Beyond

2019

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The signaling lymphocytic activation molecule (SLAM) family of receptors are expressed on the majority of immune cells. These receptors often serve as self-ligands, and play important roles in cellular communication and adhesion, thus modulating immune responses. SLAM family receptor signaling is differentially regulated in various immune cell types, with responses generally being determined by the presence or absence of two SLAM family adaptor proteins—Ewing’s sarcoma-associated transcript 2 (EAT-2) and SLAM-associated adaptor protein (SAP). In addition to serving as direct regulators of the immune system, certain SLAM family members have also been identified as direct targets for specific microbes and viruses. Here, we will discuss the known roles for these receptors in the setting of viral infection, with special emphasis placed on HIV infection. Because HIV causes such complex dysregulation of the immune system, studies of the roles for SLAM family receptors in this context are particularly exciting.

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“…Viral immune complexes were shown to promote antigen capture and dendritic cell (DC) maturation [89,90]. HIV immune complexes could also induce an antiviral state by triggering the production of type I interferon by plasmacytoid DC [91]. The enhancing effect of NAbs on adaptive antiviral immunity has yet to be fully investigated in EC, but it is interesting to note that DC from EC are more efficient at capturing HIV particles [92].…”

Section: Igg3 Are Likely Important In Nk-mediated Adcc As They Have mentioning

confidence: 99%

A role for antibodies in natural HIV control

Moris

Pereira

Chakrabarti

2019

Current Opinion in HIV and AIDS

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Purpose of the review Rare patients naturally control HIV replication without antiretroviral therapy. Understanding the mechanisms implicated in natural HIV control will inform the development of immunotherapies against HIV. Elite controllers (EC) are known for developing efficient antiviral T cell responses, but recent findings suggest that antibody (Ab) responses also play a significant role in HIV control. We review the key studies that uncovered a potent memory B cell response and highly functional anti-HIV Ab in EC, and explore the mechanisms that may account for the distinct properties of their humoral response. Recent findings EC maintain a large HIV-specific memory B cell pool that is sustained by efficient Tfh function. Neutralizing Ab rarely show high titers in controllers, but seem capable, at least in certain cases, of neutralizing contemporaneous viral strains. In addition, EC display a unique HIV-specific Ab profile in terms of isotype, antigen specificity, and glycosylation pattern, resulting in polyfunctional Ab effector functions that may promote infected cell lysis and prime effectors of the antiviral immune response.

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HIV-antibody complexes enhance production of type I interferon by plasmacytoid dendritic cells

Cited by 17 publications

References 71 publications

Sustained IFN-I Expression during Established Persistent Viral Infection: A “Bad Seed” for Protective Immunity

Sustained IFN-I Expression during Established Persistent Viral Infection: A “Bad Seed” for Protective Immunity

SLAM Family Receptor Signaling in Viral Infections: HIV and Beyond

A role for antibodies in natural HIV control

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