TY - JOUR
T1 - Memory-T-Cell-Derived Interferon-γ Instructs Potent Innate Cell Activation for Protective Immunity
AU - Soudja, Saïdi M.Homa
AU - Chandrabos, Ceena
AU - Yakob, Ernest
AU - Veenstra, Mike
AU - Palliser, Deborah
AU - Lauvau, Grégoire
N1 - Funding Information:
H2-K d /LLO 91-99 tetramers came from the NIH Tetramer Facility. We are grateful to M. Levy (AECOM) for privileged access to the FACS Aria III and thank the AECOM FACS and genomic core facilities. We thank S. Porcelli (AECOM), J. Daily (AECOM), and laboratory members L. Chorro and E. Spaulding for critical comments. Supported by the NIH (grants AI095835, AI103338, and Einstein DRC pilot to G.L.; AI099567 to D.P.; GM007288 to E.Y.). Core resources for FACS were supported by the Einstein Cancer Center (NCI cancer center support grant 2P30CA013330).
PY - 2014/6/19
Y1 - 2014/6/19
N2 - Cells of the innate immune system are essential for host defenses against primary microbial pathogen infections, yet their involvement in effective memory responses of vaccinated individuals has been poorly investigated. Here we show that memory Tcells instruct innate cells to become potent effector cells in a systemic and a mucosal model of infection. Memory Tcells controlled phagocyte, dendritic cell, and NK or NK Tcell mobilization and induction of a strong program of differentiation, which included their expression of effector cytokines and microbicidal pathways, all of which were delayed in nonvaccinated hosts. Disruption of IFN-γ signaling in Ly6C+ monocytes, dendritic cells, and macrophages impaired these processes and the control of pathogen growth. These results reveal how memory Tcells, through rapid secretion of IFN-γ, orchestrate extensive modifications of host innate immune responses that are essential for effective protection of vaccinated hosts.
AB - Cells of the innate immune system are essential for host defenses against primary microbial pathogen infections, yet their involvement in effective memory responses of vaccinated individuals has been poorly investigated. Here we show that memory Tcells instruct innate cells to become potent effector cells in a systemic and a mucosal model of infection. Memory Tcells controlled phagocyte, dendritic cell, and NK or NK Tcell mobilization and induction of a strong program of differentiation, which included their expression of effector cytokines and microbicidal pathways, all of which were delayed in nonvaccinated hosts. Disruption of IFN-γ signaling in Ly6C+ monocytes, dendritic cells, and macrophages impaired these processes and the control of pathogen growth. These results reveal how memory Tcells, through rapid secretion of IFN-γ, orchestrate extensive modifications of host innate immune responses that are essential for effective protection of vaccinated hosts.
UR - http://www.scopus.com/inward/record.url?scp=84902832196&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84902832196&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2014.05.005
DO - 10.1016/j.immuni.2014.05.005
M3 - Article
C2 - 24931122
AN - SCOPUS:84902832196
SN - 1074-7613
VL - 40
SP - 974
EP - 988
JO - Immunity
JF - Immunity
IS - 6
ER -
