The viral KSHV chemokine vMIP-II inhibits the migration of Naive and activated human NK cells by antagonizing two distinct chemokine receptors

Autor: Ariella Glasner, Noa S. Kaynan, Yoav Bauman, Shlomo Elias, Ofer Mandelboim, Alon Vitenshtein, Yotam Bar-On, Chamutal Gur, Yael Ophir, Rachel Yamin, Pinchas Tsukerman
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Viral Diseases
NK cells
Polymerase Chain Reaction
Chemokine receptor
Interleukin 21
0302 clinical medicine
NK-92
Cell Movement
Chemokine CCL5
lcsh:QH301-705.5
Cells
Cultured
0303 health sciences
Janus kinase 3
Immune cells
virus diseases
3. Good health
Cell biology
Killer Cells
Natural
Infectious Diseases
CCR5 Receptor Antagonists
Herpesvirus 8
Human
Interleukin 12
Medicine
Cytokines
Receptors
Chemokine
Chemokines
Research Article
lcsh:Immunologic diseases. Allergy
Receptors
CCR5
Anti-HIV Agents
Immunology
Immunoblotting
CX3C Chemokine Receptor 1
chemical and pharmacologic phenomena
Biology
CCL8
Microbiology
03 medical and health sciences
Virology
Genetics
CXCL10
Humans
CXCL14
Molecular Biology
030304 developmental biology
Chemokine CX3CL1
Interleukin-6
lcsh:Biology (General)
Parasitology
lcsh:RC581-607
030215 immunology
Zdroj: PLoS Pathogens, Vol 9, Iss 8, p e1003568 (2013)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: Natural killer (NK) cells are innate immune cells able to rapidly kill virus-infected and tumor cells. Two NK cell populations are found in the blood; the majority (90%) expresses the CD16 receptor and also express the CD56 protein in intermediate levels (CD56Dim CD16Pos) while the remaining 10% are CD16 negative and express CD56 in high levels (CD56Bright CD16Neg). NK cells also reside in some tissues and traffic to various infected organs through the usage of different chemokines and chemokine receptors. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human virus that has developed numerous sophisticated and versatile strategies to escape the attack of immune cells such as NK cells. Here, we investigate whether the KSHV derived cytokine (vIL-6) and chemokines (vMIP-I, vMIP-II, vMIP-III) affect NK cell activity. Using transwell migration assays, KSHV infected cells, as well as fusion and recombinant proteins, we show that out of the four cytokine/chemokines encoded by KSHV, vMIP-II is the only one that binds to the majority of NK cells, affecting their migration. We demonstrate that vMIP-II binds to two different receptors, CX3CR1 and CCR5, expressed by naïve CD56Dim CD16Pos NK cells and activated NK cells, respectively. Furthermore, we show that the binding of vMIP-II to CX3CR1 and CCR5 blocks the binding of the natural ligands of these receptors, Fractalkine (Fck) and RANTES, respectively. Finally, we show that vMIP-II inhibits the migration of naïve and activated NK cells towards Fck and RANTES. Thus, we present here a novel mechanism in which KSHV uses a unique protein that antagonizes the activity of two distinct chemokine receptors to inhibit the migration of naïve and activated NK cells.
Author Summary NK cells belong to the innate immune system, able to rapidly kill tumors and various pathogens. They reside in the blood and in various tissues and traffic to different infected organs through the usage of different chemokines and chemokine receptors. KSHV is a master of immune evasion, and around a quarter of the KSHV encoded genes are dedicated to interfere with immune cell recognition. Here, we investigate the role played by the KSHV derived cytokine and chemokines (vIL-6, vMIP-I, vMIP-II, vMIP-III) in modulating NK cell activity. We show that vMIP-II binds and inhibits the activity of two different receptors, CX3CR1 and CCR5, expressed by naïve NK cells and by activated NK cells, respectively. Thus, we demonstrate here a novel mechanism in which KSHV uses a unique protein that antagonizes the activity of two distinct chemokine receptors to inhibit the migration of naïve and activated NK cells.
Databáze: OpenAIRE
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