Interactions between Human Immunodeficiency Virus Type 1 and Polymorphonuclear Neutrophils

Casulli, Sarah; Elbim, Carole

doi:10.1159/000353588

Cited by 21 publications

(38 citation statements)

References 76 publications

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“…Neutrophils, the most abundant WBCs, have been shown to interact in various ways with HIV-1 (27,30,(81)(82)(83). In this report, we provide further evidence that neutrophils are capable of binding, transferring, and thus spreading HIV-1, although they do so less efficiently than basophils.…”

Section: Discussionsupporting

confidence: 52%

Human Blood-Circulating Basophils Capture HIV-1 and Mediate Viraltrans-Infection of CD4⁺T Cells

Jiang

Guo

et al. 2015

J Virol

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Granulocytes are a category of white blood cells (WBCs) characterized by the presence of lobulated nuclei and secretory granules in their cytoplasm. Blood-circulating granulocytes comprise mainly neutrophils, basophils, and eosinophils. Neutrophils make up the majority (50% to 60%) of circulating WBCs; basophils constitute only 0.5% to 1% and eosinophils less than 6%. Granulocytes are differentiated from bone marrow hematopoietic stem cells; they normally circulate in the bloodstream and are recruited to peripheral tissue under certain pathological conditions (1-5). Granulocytes participate in various inflammatory reactions. Basophils and eosinophils are known to modulate allergic disorders and autoimmune diseases (6-11).Granulocytes play crucial roles in combating invading pathogens. The expression by human granulocytes of a broad range of pattern recognition receptors suggests that they play a role in various forms of host innate immunity (12-14), and evidence is mounting that granulocytes are essential to the regulation of host adaptive immunity (6,15,16). Activated granulocytes release various intracellular granule proteins or cytokines to suppress or directly kill invading microbes and parasites (17)(18)(19)(20)(21)(22)(23)(24) or to recruit other host immune cells to combat pathogens. Neutrophils are "professional" phagocytes that rapidly engulf and degrade invaders or form extracellular traps to kill extracellular pathogens (23). Eosinophils have been described as capable of modulating the functions of other immune cells (16,25).The interplays between granulocytes and HIV-1 and their contribution to HIV-1 disease progression remain elusive. The majority of peripheral blood neutrophils do not express CD4 molecules on their surface. Previous work showed that 4 of 51 (7.8%) HIV-1-infected individuals and 3 of 25 (12%) uninfected individuals had CD4 expression on their peripheral blood neutrophils

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Section: Discussionsupporting

confidence: 52%

Human Blood-Circulating Basophils Capture HIV-1 and Mediate Viraltrans-Infection of CD4⁺T Cells

Jiang

Guo

et al. 2015

J Virol

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“…To date, no data to our knowledge have linked neutrophils and neutrophil-secreted proteins to the function of the mucosal barrier during HIV infection. 41 Intriguingly, 3 of 16 proteins in the identified signature were neutrophilassociated proteases (lysozyme, neutrophil collagenase, and MMP9), whereas another (Protein S100-A9) has been linked to neutrophil chemotaxis and adhesion. 42 In addition, neutrophilassociated gene set signatures were also identified within the proteomic data set, although these do not preclude the involvement of other immune cell types.…”

Section: Discussionmentioning

confidence: 99%

Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells

et al. 2016

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Elevated inflammatory cytokines (EMCs) at mucosal surfaces have been associated with HIV susceptibility, but the underlying mechanisms remain unclear. We characterized the soluble mucosal proteome associated with elevated cytokine expression in the female reproductive tract. A scoring system was devised based on the elevation (upper quartile) of at least three of seven inflammatory cytokines in cervicovaginal lavage. Using this score, HIV-uninfected Kenyan women were classified as either having EMC (n=28) or not (n=68). Of 455 proteins quantified in proteomic analyses, 53 were associated with EMC (5% false discovery rate threshold). EMCs were associated with proteases, cell motility, and actin cytoskeletal pathways, whereas protease inhibitor, epidermal cell differentiation, and cornified envelope pathways were decreased. Multivariate analysis identified an optimal signature of 16 proteins that distinguished the EMC group with 88% accuracy. Three proteins in this signature were neutrophil-associated proteases that correlated with many cytokines, especially GM-CSF (granulocyte-macrophage colony-stimulating factor), IL-1β (interleukin-1β), MIP-3α (macrophage inflammatory protein-3α), IL-17, and IL-8. Gene set enrichment analyses implicated activated immune cells; we verified experimentally that EMC women had an increased frequency of endocervical CD4(+) T cells. These data reveal strong linkages between mucosal cytokines, barrier function, proteases, and immune cell movement, and propose these as potential mechanisms that increase risk of HIV acquisition.

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“…First, if combination therapies are considered, it will be of utmost importance that the agent(s) coadministered with the passive immunotherapy do not alter neutrophil functions and counts to avoid inhibiting efficient antiviral humoral immune responses. Second, in pathological situations leading to neutropenia and/or impaired neutrophils functions, such as certain viral infections (68,69) and/or drug-induced neutropenia (70), it will be essential to restore them. This could, for example, be achieved through administration of granulocyte colony-stimulating factor (G-CSF), a cytokine already used in the clinic to treat neutropenic patients.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies

Naranjo-Gómez¹,

Lambour²,

Piechaczyk³

et al. 2018

JCI Insight

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Using a mouse retroviral model, we have shown that mAb-based immunotherapy can induce life-long endogenous protective immunity (vaccine-like effects). This observation has potentially important consequences for treating life-threatening human viral infections. Here, we investigated the role of neutrophils in this effect. Neutrophils are innate immunity effector cells with well-established microbe-killing activities that are rapidly mobilized upon infection. They are also emerging as orchestrators of innate and adaptive immunities. However, their immunomodulatory activity during antiviral mAb immunotherapies has never been studied. Our data reveal that neutrophils have an essential role in immunotherapy-induced immune protection of infected mice. Unexpectedly, neutrophils have a limited effect in controlling viral propagation upon passive immunotherapy administration, which is mostly mediated by NK cells. Instead, neutrophils operate as essential inducers of a potent host humoral antiviral response. Thus, neutrophils play an unexpected key role in protective immunity induction by antiviral mAbs. Our work opens approaches to improve antiviral immunotherapies, as it suggests that preserving neutrophil functions and counts might be required for achieving mAb-induced protective immunity.

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Interactions between Human Immunodeficiency Virus Type 1 and Polymorphonuclear Neutrophils

Cited by 21 publications

References 76 publications

Human Blood-Circulating Basophils Capture HIV-1 and Mediate Viraltrans-Infection of CD4⁺T Cells

Human Blood-Circulating Basophils Capture HIV-1 and Mediate Viraltrans-Infection of CD4⁺T Cells

Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells

Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies

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Interactions between Human Immunodeficiency Virus Type 1 and Polymorphonuclear Neutrophils

Cited by 21 publications

References 76 publications

Human Blood-Circulating Basophils Capture HIV-1 and Mediate Viraltrans-Infection of CD4+T Cells

Human Blood-Circulating Basophils Capture HIV-1 and Mediate Viraltrans-Infection of CD4+T Cells

Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells

Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies

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Human Blood-Circulating Basophils Capture HIV-1 and Mediate Viraltrans-Infection of CD4⁺T Cells

Human Blood-Circulating Basophils Capture HIV-1 and Mediate Viraltrans-Infection of CD4⁺T Cells