Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection

Lal, Kerri G.; Kim, Dohoon; Costanzo, Margaret C.; Creegan, Matthew; Leeansyah, Edwin; Dias, Joana; Paquin‐Proulx, Dominic; Eller, Leigh Anne; Schuetz, Alexandra; Phuang-Ngern, Yuwadee; Krebs, Shelly J.; Slike, Bonnie M.; Kibuuka, Hannah; Maganga, Lucas; Nitayaphan, Sorachai; Kosgei, Josphat; Sacdalan, Carlo; Ananworanich, Jintanat; Bolton, Diane L.; Michael, Nelson L.; Shacklett, Barbara L.; Robb, Merlin L.; Eller, Michael A.; Sandberg, Johan K.

doi:10.1038/s41467-019-13975-9

Cited by 42 publications

(48 citation statements)

References 61 publications

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“…Peripheral blood MAIT cells upregulated α4β7 when cocultured with mesenteric lymph node cells and 5-OP-RU, demonstrating that circulating MAIT cells can upregulate α4β7 when stimulated with antigen in the context of mesenteric lymph node cells ( 25 ). These findings are similar to what has been observed with conventional T-cells in humans and mice, where α4β7 induction is mediated by retinoic acid-producing dendritic cells from gut-associated lymphoid tissues and mesenteric lymph nodes ( 46 – 50 ). Similarly, α4β7 expression is significantly increased on peripheral MAIT cells from chronic SHIV-infected RMs, compared to naïve controls ( 27 ).…”

Section: Mucosal-associated Invariant T-cells In Acute Siv/shiv Infecsupporting

confidence: 89%

“…In humans, β7 integrin expression is increased in HIV + individuals, suggesting this relationship may be conserved between humans and NHP models [reviewed in Saeidi et al ( 51 )]. This may also partially explain the mechanism for the transient increase in MAIT cell frequencies observed in the rectal mucosa of HIV + individuals during initial infection ( 46 ). Alternatively, increased α4β7 + MAIT cells in the peripheral blood following SIV/SHIV infection may be due to expansion and subsequent trafficking of MAIT cells into the blood from mucosal tissues sites.…”

Section: Mucosal-associated Invariant T-cells In Acute Siv/shiv Infecmentioning

confidence: 99%

“…HIV infection in humans is marked by significant immune dysregulation, with significant MAIT cell depletion occurring in the peripheral circulation within the first 4 months of infection ( 33 ). However, within the first weeks of infection, longitudinal data suggests that there is a transient increase in MAIT cell frequencies in the peripheral circulation ( 46 ). Consistent with this observed MAIT cell expansion during acute HIV infection, NHP MAIT cells also appear to be activated and/or proliferating during the first month post-SIV/SHIV infection.…”

Section: Mucosal-associated Invariant T-cells In Acute Siv/shiv Infecmentioning

confidence: 99%

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Understanding the Role of Mucosal-Associated Invariant T-Cells in Non-human Primate Models of HIV Infection

2020

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Chronic HIV infection causes systemic immune activation and dysregulation, resulting in the impairment of most T-cell subsets including MAIT cells. Multiple human cohort studies demonstrate MAIT cells are selectively depleted in the peripheral blood and lymphoid tissues during HIV infection, with incomplete restoration during suppressive antiretroviral therapy. Because MAIT cells play an important role in mucosal defense against a wide array of pathogens, fully reconstituting the MAIT cell compartment in ART-treated populations could improve immunity against co-infections. Non-human primates (NHPs) are a valuable, well-described animal model for HIV infection in humans. NHPs also maintain MAIT cell frequencies more comparable to humans, compared to other common animal models, and provide a unique opportunity to study MAIT cells in the circulation and mucosal tissues in a longitudinal manner. Only recently, however, have NHP MAIT cells been thoroughly characterized using macaque-specific MR1 tetramer reagents. Here we review the similarities and differences between MAIT cells in humans and NHPs as well as the impact of SIV/SHIV infection on MAIT cells and the potential implications for future research.

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Section: Mucosal-associated Invariant T-cells In Acute Siv/shiv Infecsupporting

confidence: 89%

Section: Mucosal-associated Invariant T-cells In Acute Siv/shiv Infecmentioning

confidence: 99%

Section: Mucosal-associated Invariant T-cells In Acute Siv/shiv Infecmentioning

confidence: 99%

See 1 more Smart Citation

Understanding the Role of Mucosal-Associated Invariant T-Cells in Non-human Primate Models of HIV Infection

2020

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“…Functional assays were performed as previously described [ 19 ]. PBMCs were stimulated for a total of 24 h with IL-12 (10 ng/mL, Peprotech, Rocky Hill, NJ, USA) and IL-18 (100 ng/mL Medical & Biological Laboratories, Nagoya, Japan); monensin (eBioscience, San Diego, CA, USA) and Brefeldin A (BD Biosciences) were added during the last 6 h of stimulation.…”

Section: Methodsmentioning

confidence: 99%

Longitudinal Analysis of Peripheral and Colonic CD161+ CD4+ T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation

Lal

Phuang-Ngern

Suhkumvittaya

et al. 2020

Viruses

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CD161 expression on CD4+ T cells is associated with a Th17 functional phenotype, as well as with an innate capacity to respond to interleukin (IL)-12 and IL-18 without T cell receptor (TCR) stimulation. Chronic HIV-1 infection is associated with loss of the CD161+ CD4 T cell population, and non-human primate studies suggest that their depletion is associated with disease progression. However, the dynamics of the CD161+ CD4+ T cell population during acute HIV-1 infection remains unknown. In this study, we characterize peripheral blood CD161+ CD4+ T cells in detail, and examine how they are affected during the earliest stages of HIV-1 infection. Unbiased surface proteome screening and principal component analysis indicated that CD161+ CD4+ T cells are relatively phenotypically homogeneous between donors, and are intermediates between conventional CD4 T cells and innate-like T cells. In acute untreated HIV-1 infection, the circulating CD161+ CD4+ T cell population decreased in frequency, as did absolute cell counts starting from peak viral load, with elevated levels of activation and exhaustion markers expressed throughout acute HIV-1 infection. The capacity of these cells to respond to stimulation with IL-12 and IL-18 was also reduced. Early initiation of anti-retroviral treatment (ART) during acute HIV-1 infection restored the functionality of peripheral blood CD161+ CD4+ T cells, but not their frequency. In contrast, early ART initiation prevented the decline of colonic CD161+ CD4+ T cells that otherwise started during acute infection. Furthermore, loss of peripheral and colonic CD161+ CD4+ T cells in untreated infection was associated with levels of viral load. These results suggest that acute HIV-1 infection has profound effects on the CD161+ CD4+ T cell population that could not be completely prevented by the initiation of ART.

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“…Emerging evidence indicates that MAIT cells are innate-like sensors of viral infection; human MAIT cells are activated in response to several RNA viruses (25,26), expand during acute stages of HIV-1 infection (27), and may have a protective role in influenza virus infection as deduced from studies in murine models (28). On the basis of these distinct innate-like, tissue-homing, and proinflammatory characteristics of MAIT cells, we set out to study these cells in COVID-19.…”

Section: Introductionmentioning

confidence: 99%

MAIT cell activation and dynamics associated with COVID-19 disease severity

et al. 2020

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Severe COVID-19 is characterized by excessive inflammation of the lower airways. The balance of protective versus pathological immune responses in COVID-19 is incompletely understood. Mucosa-associated invariant T (MAIT) cells are antimicrobial T cells that recognize bacterial metabolites, and can also function as innate-like sensors and mediators of antiviral responses. Here, we investigated the MAIT cell compartment in COVID-19 patients with moderate and severe disease, as well as in convalescence. We show profound and preferential decline in MAIT cells in the circulation of patients with active disease paired with strong activation. Furthermore, transcriptomic analyses indicated significant MAIT cell enrichment and pro-inflammatory IL-17A bias in the airways. Unsupervised analysis identified MAIT cell CD69high and CXCR3low immunotypes associated with poor clinical outcome. MAIT cell levels normalized in the convalescent phase, consistent with dynamic recruitment to the tissues and later release back into the circulation when disease is resolved. These findings indicate that MAIT cells are engaged in the immune response against SARS-CoV-2 and suggest their possible involvement in COVID-19 immunopathogenesis.

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Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection

Cited by 42 publications

References 61 publications

Understanding the Role of Mucosal-Associated Invariant T-Cells in Non-human Primate Models of HIV Infection

Understanding the Role of Mucosal-Associated Invariant T-Cells in Non-human Primate Models of HIV Infection

Longitudinal Analysis of Peripheral and Colonic CD161+ CD4+ T Cell Dysfunction in Acute HIV-1 Infection and Effects of Early Treatment Initiation

MAIT cell activation and dynamics associated with COVID-19 disease severity

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