Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells

Julio Alberti; Jesus G. Valenzuela; Vern B. Carruthers; Sara Hieny; John Andersen; Hugues Charest; Caetano Reis E Sousa; Alan Fairlamb; Jose M. Ribeiro; Alan Sher

doi:10.1038/ni915

Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells

Julio Alberti (Lead / Corresponding author)
, Jesus G. Valenzuela
, Vern B. Carruthers
, Sara Hieny
, John Andersen
, Hugues Charest
, Caetano Reis E Sousa
, Alan Fairlamb
, Jose M. Ribeiro
, Alan Sher

Research output: Contribution to journal › Article › peer-review

215 Citations (Scopus)

Abstract

Toxoplasma gondii releases factors that potently stimulate production of interleukin-12 (IL-12) from dendritic cells (DCs). Purification of this activity showed that cyclophilin-18 (C-18) was its principal component, and antibodies generated against recombinant C-18 inhibited tachyzoite extract-induced synthesis of IL-12. Recombinant C-18 showed high affinity for and triggered cell signaling through CCR5, a chemokine receptor important in parasite-induced IL-12 production by DCs. These findings suggest that the unusual potency of T gondii in inducing IL-12 from DCs results from its synthesis of a unique chemokine mimic that signals through CCR5. The ability to generate this strong protective response may benefit parasite transmission by preventing the protozoan from overwhelming its intermediate hosts.

Original language	English
Pages (from-to)	485-490
Number of pages	6
Journal	Nature Immunology
Volume	4
Issue number	5
DOIs	https://doi.org/10.1038/ni915
Publication status	Published - May 2003

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

IMMUNITY
IMMUNOPHILINS
INTERLEUKIN-12
CHEMOKINE RECEPTOR
ANTIGEN
MALARIA
BIOCHEMICAL-CHARACTERIZATION
TOXOPLASMA-GONDII
RESISTANCE
CYCLOPHILIN

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10.1038/ni915

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@article{fc7ce654af2a42069683251beae9ce20,

title = "Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells",

abstract = "Toxoplasma gondii releases factors that potently stimulate production of interleukin-12 (IL-12) from dendritic cells (DCs). Purification of this activity showed that cyclophilin-18 (C-18) was its principal component, and antibodies generated against recombinant C-18 inhibited tachyzoite extract-induced synthesis of IL-12. Recombinant C-18 showed high affinity for and triggered cell signaling through CCR5, a chemokine receptor important in parasite-induced IL-12 production by DCs. These findings suggest that the unusual potency of T gondii in inducing IL-12 from DCs results from its synthesis of a unique chemokine mimic that signals through CCR5. The ability to generate this strong protective response may benefit parasite transmission by preventing the protozoan from overwhelming its intermediate hosts.",

keywords = "IMMUNITY, IMMUNOPHILINS, INTERLEUKIN-12, CHEMOKINE RECEPTOR, ANTIGEN, MALARIA, BIOCHEMICAL-CHARACTERIZATION, TOXOPLASMA-GONDII, RESISTANCE, CYCLOPHILIN",

author = "Julio Alberti and Valenzuela, \{Jesus G.\} and Carruthers, \{Vern B.\} and Sara Hieny and John Andersen and Hugues Charest and Sousa, \{Caetano Reis E\} and Alan Fairlamb and Ribeiro, \{Jose M.\} and Alan Sher",

year = "2003",

month = may,

doi = "10.1038/ni915",

language = "English",

volume = "4",

pages = "485--490",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Research",

number = "5",

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TY - JOUR

T1 - Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells

AU - Alberti, Julio

AU - Valenzuela, Jesus G.

AU - Carruthers, Vern B.

AU - Hieny, Sara

AU - Andersen, John

AU - Charest, Hugues

AU - Sousa, Caetano Reis E

AU - Fairlamb, Alan

AU - Ribeiro, Jose M.

AU - Sher, Alan

PY - 2003/5

Y1 - 2003/5

N2 - Toxoplasma gondii releases factors that potently stimulate production of interleukin-12 (IL-12) from dendritic cells (DCs). Purification of this activity showed that cyclophilin-18 (C-18) was its principal component, and antibodies generated against recombinant C-18 inhibited tachyzoite extract-induced synthesis of IL-12. Recombinant C-18 showed high affinity for and triggered cell signaling through CCR5, a chemokine receptor important in parasite-induced IL-12 production by DCs. These findings suggest that the unusual potency of T gondii in inducing IL-12 from DCs results from its synthesis of a unique chemokine mimic that signals through CCR5. The ability to generate this strong protective response may benefit parasite transmission by preventing the protozoan from overwhelming its intermediate hosts.

AB - Toxoplasma gondii releases factors that potently stimulate production of interleukin-12 (IL-12) from dendritic cells (DCs). Purification of this activity showed that cyclophilin-18 (C-18) was its principal component, and antibodies generated against recombinant C-18 inhibited tachyzoite extract-induced synthesis of IL-12. Recombinant C-18 showed high affinity for and triggered cell signaling through CCR5, a chemokine receptor important in parasite-induced IL-12 production by DCs. These findings suggest that the unusual potency of T gondii in inducing IL-12 from DCs results from its synthesis of a unique chemokine mimic that signals through CCR5. The ability to generate this strong protective response may benefit parasite transmission by preventing the protozoan from overwhelming its intermediate hosts.

KW - IMMUNITY

KW - IMMUNOPHILINS

KW - INTERLEUKIN-12

KW - CHEMOKINE RECEPTOR

KW - ANTIGEN

KW - MALARIA

KW - BIOCHEMICAL-CHARACTERIZATION

KW - TOXOPLASMA-GONDII

KW - RESISTANCE

KW - CYCLOPHILIN

U2 - 10.1038/ni915

DO - 10.1038/ni915

M3 - Article

SN - 1529-2908

VL - 4

SP - 485

EP - 490

JO - Nature Immunology

JF - Nature Immunology

IS - 5

ER -

Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells

Abstract

UN SDGs

Keywords

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