NK cells, displaying early activation, cytotoxicity and adhesion molecules, are associated with mild dengue disease

Azeredo, Elzinandes Leal de; Oliveira-Pinto, Luzia Maria de; Zagne, S.M.O.; Cerqueira, Denise; Nogueira, Rita MR; Kubelka, Claire Fernandes

doi:10.1111/j.1365-2249.2006.02996.x

Cited by 117 publications

(122 citation statements)

References 74 publications

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“…In our DENV model, we see MC-dependent infiltration of NK1.1 + cells, subsets of which also expressed T-cell markers. Although NKT cells have long been associated with antiviral immunity and were reported to increase in the blood of DENV-infected human patients (15), their role in DENV infection has not been adequately explored. For example, a large percentage of virusspecific CD8 + and CD4 + T cells in a lymphocytic choriomeningitis virus model had an NKT phenotype (38), and NKT cells have been shown to be protective in models of herpes, respiratory syncytial, and hepatitis B viruses (39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

“…During the progression of infection, DENV travels to draining lymph nodes (DLNs) and can subsequently establish viremia in the host (12). Cells that can kill DENVinfected cells, such as natural killer (NK) cells and T cells, have been implicated in DENV clearance in vivo (13)(14)(15), yet the cell types involved in initial surveillance for DENV are less defined. MCs are prevalent in the skin and, therefore, are likely to be among the first immune cells to encounter s.c.-injected DENV.…”

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confidence: 99%

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Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance

John

Rathore

Yap

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

188

244

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A wealth of evidence supports the essential contributions of mast cells (MCs) to immune defense against bacteria and parasites; however, the role of MCs in viral infections has not been defined. We now report that rodent, monkey, and human MCs are able to detect dengue virus (DENV), a lymphotropic, enveloped, singlestranded, positive-sense RNA virus that results in MC activation and degranulation. We observe that the response of MCs to DENV also involves the activation of antiviral intracellular host response pathways, melanoma differentiation-associated gene 5 (MDA5) and retinoic acid inducible gene 1 (RIG-I), and the de novo transcription of cytokines, including TNF-α and IFN-α, and chemokines, such as CCL5, CXCL12, and CX3CL1. This multifaceted response of MCs to DENV is consequential to the containment of DENV in vivo because, after s.c. infection, MC-deficient mice show increased viral burden within draining lymph nodes, which are known to be targeted organs during DENV spread, compared with MC-sufficient mice. This containment of DENV is linked to the MC-driven recruitment of natural killer and natural killer T cells into the infected skin. These findings support expanding the defined role of immunosurveillance by MCs to include viral pathogens.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance

John

Rathore

Yap

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

188

244

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“…ese mechanisms could play a protective role in the immunopathology of DHF by the early and efficient clearance of DENV by direct or indirect NK functions thereby limiting viral replication and its attended cascading cytokine mediated plasma leakage. NK cells have been associated with mild dengue [28,29].…”

Section: 2mentioning

confidence: 99%

Pathogenesis of Dengue Haemorrhagic Fever and Its Impact on Case Management

Sellahewa

2013

ISRN Infectious Diseases

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Plasma leakage and intrinsic coagulopathy are the pathological hall marks in dengue haemorrhagic fever (DHF). Viral virulence, infection enhancing antibodies, cytokines and chemical mediators in the setting of intense immune activation are the key players implicated in the pathogenesis of DHF; the exact nature of which is yet to be fully understood. e pathophysiological changes the attended clinical features of plasma leakage necessitate recognition of changing physiological parameters for the early recognition of plasma leakage and appropriate �uid therapy. On the other hand, the changes in the haematological indices resulting from coagulopathy can tempt the clinician to initiate other modalities of therapy. A clearer understanding of the pathogenesis of DHF and the appreciation that both of these fundamental pathological changes share common pathogenic mechanisms would facilitate the appropriateness of management decisions and the early recognition of severe disease. us, thrombocytopaenia, reduced �brinogen, and prolonged partial thromboplastin time early in the disease course connoted severe disease and attended plasma leakage rather than clinical bleeding. e detection of plasma cytokine pro�le by a multiple bead immunoassay could also complement clinical parameters in predicting severe disease early in the disease course. us, MIP-indicates good prognosis while IFN-portends severe disease.

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“…More recently, our group demonstrated that peripheral NK and NKT cells rates are increased in adult Brazilian mild dengue patients. The majority of these NK cells display early markers for activation (CD69, HLA-DR, and CD38), cell adhesion molecules (CD44, CD11a) besides the intracellular cytotoxic granule, Tia-1 (Azeredo et al 2006). A study displayed that during acute infection few DENV-specific T cells of low affinity for the infecting virus were recovered in Thai children, contributing to higher viral loads and increased immunopathology (Mongkolsapaya et al 2003).…”

mentioning

confidence: 99%

Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease

Azeredo¹,

Zagne

Alvarenga³

et al. 2006

Mem. Inst. Oswaldo Cruz

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NK cells, displaying early activation, cytotoxicity and adhesion molecules, are associated with mild dengue disease

Cited by 117 publications

References 74 publications

Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance

Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance

Pathogenesis of Dengue Haemorrhagic Fever and Its Impact on Case Management

Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease

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