SLAMF7 Is a Critical Negative Regulator of IFN-α–Mediated CXCL10 Production in Chronic HIV Infection

O’Connell, Patrick M.; Pepelyayeva, Yuliya; Blake, Maja K.; Hyslop, Sean; Crawford, R. J.; Rizzo, Michael D.; Pereira-Hicks, Cristiane; Godbehere, Sarah; Dale, Linda; Gulick, Peter; Kaminski, Norbert E.; Amalfitano, Andrea; Aldhamen, Yasser A.

doi:10.4049/jimmunol.1800847

Cited by 33 publications

(54 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the hyper-acute monocyte responses (Fig. 4C), we found a small set of upregulated genes shared only by P3 and P4, including SLAMF7 , whose activation was recently described to downregulate CCR5 on monocytes and reduced their infection capacity by HIV 83 , suggesting a potential difference in monocyte susceptibility and phenotype in these individuals during hyper-acute infection. Moreover, referring back to the initial cell type clustering of our data (Fig.…”

Section: Resultsmentioning

confidence: 78%

Integrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection

Kazer

Aicher

Muema

et al. 2019

Preprint

View full text Add to dashboard Cite

30Cellular immunity is critical for controlling intracellular pathogens, but the dynamics and 31 cooperativity of the evolving host response to infection are not well defined. Here, we apply single-32 cell RNA-sequencing to longitudinally profile pre-and immediately post-HIV infection peripheral 33 immune responses of multiple cell types in four untreated individuals. Onset of viremia induces a 34 strong transcriptional interferon response integrated across most cell types, with subsequent pro-35 inflammatory T cell differentiation, monocyte MHC-II upregulation, and cytolytic killing. With 36 longitudinal sampling, we nominate key intra-and extracellular drivers that induce these 37 programs, and assign their multi-cellular targets, temporal ordering, and duration in acute 38 infection. Two individuals studied developed spontaneous viral control, associated with initial 39 elevated frequencies of proliferating cytotoxic cells, inclusive of a previously unappreciated 40 proliferating natural killer (NK) cell subset. Our study presents a unified framework for 41 characterizing immune evolution during a persistent human viral infection at single-cell resolution, 42 and highlights programs that may drive response coordination and influence clinical trajectory. 43 44 54Recently, high-throughput single-cell RNA-sequencing (scRNA-Seq) has emerged as a 55 powerful tool to characterize, transcriptome-wide, complex human systems in health and disease 56 at single-cell resolution [3][4][5][6][7][8][9] . When applied to a collection of samples across a disease setting, this 57 approach provides a platform for investigating cell types, states, interactions, and drivers 58 associated with that disease; this information can be used to develop testable hypotheses on 59 therapeutic modulations that may ameliorate disease state 7,8 . Meanwhile, within an individual, 60longitudinal sampling provides an opportunity to decipher, at unprecedented resolution and 61 absent potentially confounding inter-individual variability 7 , shifts in these same variables, and to 62 3 associate observed changes with internal or external perturbations 10-12 . Such sampling of a host's 63 exposure to a pathogen could provide foundational insights into essential cellular response 64 features and their coordination, empowering the rational design of improved prophylactic 65 interventions. 66Illustratively, a better understanding of the interplay between innate and adaptive immune 67 responses at the very earliest stages of a viral infection, and its impact on long-term disease, 68 could reveal principles to accelerate prevention efforts. Human Immunodeficiency Virus (HIV) has 69 been the subject of thorough study, and thus is a well-considered model system for examining 70 host responses to a pathogen. Moreover, although the development of antiretroviral therapy 71 (ART) 13 , as well as implementation of pre-exposure prophylaxis (PrEP) 14 and combination 72 prevention efforts, has improved the lives of persons living with HIV, increased life expectancie...

show abstract

Section: Resultsmentioning

confidence: 78%

Integrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection

Kazer

Aicher

Muema

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Signaling through these well-studied pathways produces a host of pro-inflammatory cytokines, chemokines, and viral restriction factors to help combat early infection [14]. Importantly, myeloid cell responses to PRR activation can be tuned based on signaling from SLAMF1, SLAMF5, SLAMF7, SLAMF8, and SLAMF9 [15][16][17][18][19][20][21]. Therefore, the specific microenvironment, including other immune cells interacting with PRR-responding myeloid cells, is essential for tuning myeloid cell responses by SLAMF family-dependent mechanisms.…”

Section: Immune Responses To Viral Infectionsmentioning

confidence: 99%

“…Regulates monocyte responses to type I interferons [18] Regulates monocyte susceptibility to HIV-1 infection [18] NK cells, CD4 + T cells, CD8 + T cells, NKT cells, classical monocytes, inflammatory monocytes, macrophages, DCs, B cells, plasma cells…”

Section: Slamf7 (Cracc Cd319 Cs1)mentioning

confidence: 99%

“…It is hard to compare this study to the two previously mentioned studies, as those were performed using primary human cells and this study used a murine model. Differences in immune responses to signaling from various members of the SLAM family has been noted between human and murine immune cells [18,44]. SLAMF1 has also been described to have a specific role in T cells.…”

Section: Slamf9 (Sf2001 Cd84h1)mentioning

confidence: 99%

“…SLAMF7 is expressed on NK cells, CD4 + T cells (low levels), CD8 + T cells, NKT cells, classical monocytes (low levels), inflammatory monocytes (high levels), macrophages, DCs, B cells, and plasma cells. It is notably absent on granulocytes [1,18]. SLAMF7 signaling is less complex than other SLAM family members in that its ITSM can only bind to EAT-2, and not SAP In the presence of EAT-2 it performs functions that can generally be described as activating, and in the absence of EAT-2 it recruits a number of inhibitory phosphates (SHP-1, SHP-2, SHIP-1, CD45, and csk) to inhibit cellular functions [81][82][83].…”

Section: Slamf7 (Cracc Cs1 Cd319)mentioning

confidence: 99%

See 2 more Smart Citations

SLAM Family Receptor Signaling in Viral Infections: HIV and Beyond

2019

View full text Add to dashboard Cite

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.

show abstract

Nasopharyngeal neutrophilic‐retention signatures could predict disease progression in early SARS‐CoV‐2 infection

Qi,

Cao,

Shen

et al. 2023

Journal of Medical Virology

View full text Add to dashboard Cite

The nasopharynx is the initial site of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, and neutrophils play a critical role in preventing viral transmission into the lower airways or lungs during the early phases of infection. However, neutrophil dynamics, functional signatures, and predictive roles in the nasopharynx of coronavirus disease 2019 (COVID‐19) patients have not yet been elucidated. In this study, we carried out RNA sequencing of nasopharyngeal swabs from a cohort of COVID‐19 patients with mild, moderate, severe outcomes and healthy donors as controls. Over 32.7% of the differentially expressed genes associated with COVID‐19 severity were neutrophil‐related, including those involved in migration, neutrophil extracellular traps formation, and inflammasome activation. Multicohort single‐cell RNA sequencing analysis further confirmed these findings and identified a population of neutrophils expressing Vacuolar‐type ATPase (V‐ATPase) and the chemokine receptor CXCR4 in the nasopharynx. This population of neutrophils preferentially expressed pro‐inflammatory genes relevant to phagosomal maturation as well as local reactive oxygen species and reactive nitrogen species production in the nasopharynx of patients with severe outcomes. A four‐gene panel defined as a neutrophil signature associated with COVID‐19 progression (NSAP) was identified as an early diagnostic predictor of severe COVID‐19, which potentially distinguished severe patients from mild cases with influenza, respiratory syncytial virus, dengue virus, or hepatitis B virus infection. NSAP is mainly expressed on CXCR4high neutrophils and exhibits a significant association with the cell fraction of this neutrophil population. This study highlights novel potential therapeutic targets or diagnostic tools for predicting patients at a higher risk of severe outcomes.

show abstract

SLAMF7 Is a Critical Negative Regulator of IFN-α–Mediated CXCL10 Production in Chronic HIV Infection

Cited by 33 publications

References 65 publications

Integrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection

Integrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection

SLAM Family Receptor Signaling in Viral Infections: HIV and Beyond

Nasopharyngeal neutrophilic‐retention signatures could predict disease progression in early SARS‐CoV‐2 infection

Contact Info

Product

Resources

About