TLR2 on blood monocytes senses dengue virus infection and its expression correlates with disease pathogenesis

Aguilar-Briseño, José Alberto; Upasani, Vinit; Ellen, Bram M. ter; Moser, Jill; Paužuolis, Mindaugas; Silva, Mariana Ruiz; Sothy, Heng; Laurent, Denis; Choeung, Rithy; Dussart, Philippe; Cantaert, Tineke; Smit, Jolanda M.; Rodenhuis-Zybert, Izabela A.

doi:10.1038/s41467-020-16849-7

Cited by 47 publications

(60 citation statements)

References 86 publications

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“…The primers were obtained from Applied Biosystems, including IL-8 (Hs00174103_m1), GM-CSF (Hs00929873_m1), ICAM-1 (Hs00164932_m1), IL-1β (Hs00174097_m1) and 18s RNA (Hs99999901_s1). All primers were optimized for TaqMan PCR and referenced in recent studies 56 – 60 .…”

Section: Methodsmentioning

confidence: 99%

HIV induces airway basal progenitor cells to adopt an inflammatory phenotype

Chung

Khan

Kaner

et al. 2021

Sci Rep

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Despite the introduction of anti-retroviral therapy, chronic HIV infection is associated with an increased incidence of other comorbidities such as COPD. Based on the knowledge that binding of HIV to human airway basal stem/progenitor cells (BC) induces a destructive phenotype by increased MMP-9 expression through MAPK signaling pathways, we hypothesized that HIV induces the BC to express inflammatory mediators that contribute to the pathogenesis of emphysema. Our data demonstrate that airway BC isolated from HAART-treated HIV+ nonsmokers spontaneously release inflammatory mediators IL-8, IL-1β, ICAM-1 and GM-CSF. Similarly, exposure of normal BC to HIV in vitro up-regulates expression of the same inflammatory mediators. These HIV-BC derived mediators induce migration of alveolar macrophages (AM) and neutrophils and stimulate AM proliferation. This HIV-induced inflammatory phenotype likely contributes to lung inflammation in HIV+ individuals and provides explanation for the increased incidence of COPD in HIV+ individuals.

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Section: Methodsmentioning

confidence: 99%

HIV induces airway basal progenitor cells to adopt an inflammatory phenotype

Chung

Khan

Kaner

et al. 2021

Sci Rep

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“…Progression to severe hemorrhagic shock in DENV infection is also marked by upregulation of CD14+CD16+ monocytes expressing CD163 ( 85 ). DENV infection in monocytes is detected by TLR2/6, with CD14 acting as a co-receptor, resulting in the induction of pro-inflammatory cytokine expression via NF-κB signaling pathway ( 86 ).…”

Section: Viral Pattern Recognition Receptors In Dysregulated Cytokinementioning

confidence: 99%

Severe Clinical Worsening in COVID-19 and Potential Mechanisms of Immune-Enhanced Disease

Hussman

2021

Front. Med.

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Infection by the novel SARS-CoV-2 coronavirus produces a range of outcomes, with the majority of cases producing mild or asymptomatic effects, and a smaller subset progressing to critical or fatal COVID-19 disease featuring severe acute respiratory distress. Although the mechanisms driving severe disease progression remain unknown, it is possible that the abrupt clinical deterioration observed in patients with critical disease corresponds to a discrete underlying expansion of viral tropism, from infection of cells comprising respiratory linings and alveolar epithelia to direct infection and activation of inflammatory monocytes and macrophages. Dysregulated immune responses could then contribute to disease severity. This article discusses the potential role of monocyte/macrophage (Mo/Mϕ) infection by SARS-CoV-2 in mediating the immune response in severe COVID-19. Additional mechanisms of immune-enhanced disease, comprising maladaptive immune responses that may aggravate rather than alleviate severity, are also discussed. Severe acute clinical worsening in COVID-19 patients may be influenced by the emergence of antibodies that participate in hyperinflammatory monocyte response, release of neutrophil extracellular traps (NETs), thrombosis, platelet apoptosis, viral entry into Fc gamma receptor (FcγR)-expressing immune cells, and induction of autoantibodies with cross-reactivity against host proteins. While the potential roles of Mo/Mϕ infection and immune-enhanced pathology in COVID-19 are consistent with a broad range of clinical and laboratory findings, their prominence remains tentative pending further validation. In the interim, these proposed mechanisms present immediate avenues of inquiry that may help to evaluate the safety of candidate vaccines and antibody-based therapeutics, and to support consideration of pathway-informed, well-tolerated therapeutic candidates targeting the dysregulated immune response.

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“…To determine whether there was a change in the number of leukocytes, we next examined CBCs after DENV-WB coculture for 24 h. We found an increase in the number of neutrophils in the DENV group (DENV, 56.80 ± 7.37%; mock, 44.52 ± 9.26%) and a decrease in the number of monocytes in the DENV group (DENV, 0.908 ± 0.30%; mock, 4.37 ± 1.66%) ( Figure 3 ). Monocytes are the most critical blood mononuclear phagocyte and one of the leading cell targets of DENV [ 31 , 32 ]. The results showed a decrease in the number of monocytes caused by DENV ex vivo .…”

Section: Resultsmentioning

confidence: 99%

Increased TNF-α Initiates Cytoplasmic Vacuolization in Whole Blood Coculture with Dengue Virus

Huang

Jhan

Shen

et al. 2021

Journal of Immunology Research

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During the acute febrile phase of dengue virus (DENV) infection, viremia can cause severe systemic immune responses accompanied by hematologic disorders. This study investigated the potential induction and mechanism of the cytopathic effects of DENV on peripheral blood cells ex vivo. At one day postinfection, there was viral nonstructural protein NS1 but no further virus replication measured in the whole blood culture. Notably, DENV exposure caused significant vacuolization in monocytic phagocytes. With a minor change in the complete blood cell count, except for a minor increase in neutrophils and a significant decrease in monocytes, the immune profiling assay identified several changes, particularly a significant reduction in CD14-positive monocytes as well as CD11c-positive dendritic cells. Abnormal production of TNF-α was highly associated with the induction of vacuolization. Manipulating TNF-α expression resulted in cytopathogenic effects. These results demonstrate the potential hematological damage caused by ex vivo DENV-induced TNF-α.

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TLR2 on blood monocytes senses dengue virus infection and its expression correlates with disease pathogenesis

Cited by 47 publications

References 86 publications

HIV induces airway basal progenitor cells to adopt an inflammatory phenotype

HIV induces airway basal progenitor cells to adopt an inflammatory phenotype

Severe Clinical Worsening in COVID-19 and Potential Mechanisms of Immune-Enhanced Disease

Increased TNF-α Initiates Cytoplasmic Vacuolization in Whole Blood Coculture with Dengue Virus

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