TY - JOUR
T1 - Cross-Talk in the Innate Immune System
T2 - Neutrophils Instruct Recruitment and Activation of Dendritic Cells during Microbial Infection
AU - Bennouna, Soumaya
AU - Bliss, Susan K.
AU - Curiel, Tyler J.
AU - Denkers, Eric Y.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/12/1
Y1 - 2003/12/1
N2 - Type I inflammatory cytokines are essential for immunity to many microbial pathogens, including Toxoplasma gondii. Dendritic cells (DC) are key to initiating type 1 immunity, but neutrophils are also a source of chemokines and cytokines involved in Th1 response ignition. We found that T. gondii triggered neutrophil synthesis of CC chemokine ligand (CCL)3, CCL4, CCL5, and CCL20, chemokines that were strongly chemotactic for immature DC. Moreover, supernatants obtained from parasite-stimulated polymorphonuclear leukocytes induced DC IL-12(p40) and TNF-α production. Parasite-triggered neutrophils also released factors that induced DC CD40 and CD86 up-regulation, and this response was dependent upon parasite-triggered neutrophil TNF-α production. In vivo evidence that polymorphonuclear leukocytes exert an important influence on DC activation was obtained by examining splenic DC cytokine production following infection of neutrophil-depleted mice. These animals displayed severely curtailed splenic DC IL-12 and TNF-α production, as revealed by ex vivo flow cytometric analysis and in vitro culture assay. Our results reveal a previously unrecognized regulatory role for neutrophils in DC function during microbial infection, and suggest that cross-talk between these cell populations is an important component of the innate immune response to infection.
AB - Type I inflammatory cytokines are essential for immunity to many microbial pathogens, including Toxoplasma gondii. Dendritic cells (DC) are key to initiating type 1 immunity, but neutrophils are also a source of chemokines and cytokines involved in Th1 response ignition. We found that T. gondii triggered neutrophil synthesis of CC chemokine ligand (CCL)3, CCL4, CCL5, and CCL20, chemokines that were strongly chemotactic for immature DC. Moreover, supernatants obtained from parasite-stimulated polymorphonuclear leukocytes induced DC IL-12(p40) and TNF-α production. Parasite-triggered neutrophils also released factors that induced DC CD40 and CD86 up-regulation, and this response was dependent upon parasite-triggered neutrophil TNF-α production. In vivo evidence that polymorphonuclear leukocytes exert an important influence on DC activation was obtained by examining splenic DC cytokine production following infection of neutrophil-depleted mice. These animals displayed severely curtailed splenic DC IL-12 and TNF-α production, as revealed by ex vivo flow cytometric analysis and in vitro culture assay. Our results reveal a previously unrecognized regulatory role for neutrophils in DC function during microbial infection, and suggest that cross-talk between these cell populations is an important component of the innate immune response to infection.
UR - http://www.scopus.com/inward/record.url?scp=0345690207&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0345690207&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.171.11.6052
DO - 10.4049/jimmunol.171.11.6052
M3 - Article
C2 - 14634118
AN - SCOPUS:0345690207
VL - 171
SP - 6052
EP - 6058
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 11
ER -