TY - JOUR
T1 - Human neutrophil-expressed CD28 interacts with macrophage B7 to induce phosphatidylinositol 3-kinase-dependent IFN-γ secretion and restriction of Leishmania growth
AU - Venuprasad, K.
AU - Banerjee, Pinaki P.
AU - Chattopadhyay, Subhasis
AU - Sharma, Satyan
AU - Pal, Subrata
AU - Parab, P. B.
AU - Mitra, Debashis
AU - Saha, Bhaskar
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2002/7/15
Y1 - 2002/7/15
N2 - We previously showed that CD28 is expressed on human peripheral blood neutrophils and plays an important role in CXCR-1 expression and IL-8-induced neutrophil migration. In this work we demonstrate that Leishmania major infection of macrophages results in parasite dose-dependent IL-8 secretion in vitro and in IL-8-directed neutrophil migration, as blocked by both anti-IL-8 and anti-IL-8R Abs, toward the L. major-infected macrophages. In the neutrophil-macrophage cocultures, both CTLA4-Ig, a fusion protein that blocks CD28-CD80/CD86 interaction, and a neutralizing anti-IFN-γ Ab inhibit the anti-leishmanial function of neutrophils, suggesting that the neutrophil-macrophage interaction via CD28-CD80/CD86 plays an important role in the IFN-γ-dependent restriction of the parasite growth. Cross-linking of neutrophil-expressed CD28 by monoclonal anti-CD28 Ab or B7.1-Ig or B7.2-Ig results in phosphatidylinositol 3-kinase association with CD28 and in wortmannin-sensitive but cyclosporin A-resistant induction and secretion of IFN-γ. Whereas the neutrophils secrete IFN-γ with CD28 signal alone, the T cells do not secrete the cytokine in detectable amounts with the same signal. Thus, neutrophil-expressed CD28 modulates not only the granulocyte migration but also induction and secretion of IFN-γ at the site of infection where it migrates from the circulation.
AB - We previously showed that CD28 is expressed on human peripheral blood neutrophils and plays an important role in CXCR-1 expression and IL-8-induced neutrophil migration. In this work we demonstrate that Leishmania major infection of macrophages results in parasite dose-dependent IL-8 secretion in vitro and in IL-8-directed neutrophil migration, as blocked by both anti-IL-8 and anti-IL-8R Abs, toward the L. major-infected macrophages. In the neutrophil-macrophage cocultures, both CTLA4-Ig, a fusion protein that blocks CD28-CD80/CD86 interaction, and a neutralizing anti-IFN-γ Ab inhibit the anti-leishmanial function of neutrophils, suggesting that the neutrophil-macrophage interaction via CD28-CD80/CD86 plays an important role in the IFN-γ-dependent restriction of the parasite growth. Cross-linking of neutrophil-expressed CD28 by monoclonal anti-CD28 Ab or B7.1-Ig or B7.2-Ig results in phosphatidylinositol 3-kinase association with CD28 and in wortmannin-sensitive but cyclosporin A-resistant induction and secretion of IFN-γ. Whereas the neutrophils secrete IFN-γ with CD28 signal alone, the T cells do not secrete the cytokine in detectable amounts with the same signal. Thus, neutrophil-expressed CD28 modulates not only the granulocyte migration but also induction and secretion of IFN-γ at the site of infection where it migrates from the circulation.
UR - http://www.scopus.com/inward/record.url?scp=0037100437&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037100437&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.169.2.920
DO - 10.4049/jimmunol.169.2.920
M3 - Article
C2 - 12097397
AN - SCOPUS:0037100437
SN - 0022-1767
VL - 169
SP - 920
EP - 928
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -