CXCR3-dependent CD4⺠T cells are required to activate inflammatory monocytes for defense against intestinal infection.
PLoS Pathog
; 9(10): e1003706, 2013.
Article
in En
| MEDLINE
| ID: mdl-24130498
ABSTRACT
Chemokines and their receptors play a critical role in orchestrating immunity to microbial pathogens, including the orally acquired Th1-inducing protozoan parasite Toxoplasma gondii. Chemokine receptor CXCR3 is associated with Th1 responses, and here we use bicistronic CXCR3-eGFP knock-in reporter mice to demonstrate upregulation of this chemokine receptor on CD4⺠and CD8⺠T lymphocytes during Toxoplasma infection. We show a critical role for CXCR3 in resistance to the parasite in the intestinal mucosa. Absence of the receptor in Cxcr3â»/â» mice resulted in selective loss of ability to control T. gondii specifically in the lamina propria compartment. CD4⺠T cells were impaired both in their recruitment to the intestinal lamina propria and in their ability to secrete IFN-γ upon stimulation. Local recruitment of CD11bâºLy6C/G⺠inflammatory monocytes, recently reported to be major anti-Toxoplasma effectors in the intestine, was not impacted by loss of CXCR3. However, inflammatory monocyte activation status, as measured by dual production of TNF-α and IL-12, was severely impaired in Cxcr3â»/â» mice. Strikingly, adoptive transfer of wild-type but not Ifnγâ»/â» CD4⺠T lymphocytes into Cxcr3â»/â» animals prior to infection corrected the defect in inflammatory macrophage activation, simultaneously reversing the susceptibility phenotype of the knockout animals. Our results establish a central role for CXCR3 in coordinating innate and adaptive immunity, ensuring generation of Th1 effectors and their trafficking to the frontline of infection to program microbial killing by inflammatory monocytes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Toxoplasma
/
Monocytes
/
Toxoplasmosis
/
Th1 Cells
/
Receptors, CXCR3
/
Immunity, Cellular
/
Immunity, Innate
/
Intestinal Diseases
Limits:
Animals
Language:
En
Journal:
PLoS Pathog
Year:
2013
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA