Relative contributions of dectin-1 and complement to immune responses to particulate β-glucans.
Glucan particles (GPs) are Saccharomyces cerevisiae cell walls chemically extracted so they are composed primarily of particulate β-1,3-D-glucans. GPs are recognized by Dectin-1 and are potent complement activators. Mice immunized with Ag-loaded GPs develop robust Ab and CD4(+) T cell responses. In this study, we examined the relative contributions of Dectin-1 and complement to GP phagocytosis and Ag-specific responses to immunization with OVA encapsulated in GPs. The in vitro phagocytosis of GPs by bone marrow-derived dendritic cells was facilitated by heat-labile serum component(s) independently of Dectin-1. This enhanced uptake was not seen with serum from complement component 3 knockout (C3(-/-)) mice and was also inhibited by blocking Abs directed against complement receptor 3. After i.p. injection, percent phagocytosis of GPs by peritoneal macrophages was comparable in wild-type and Dectin-1(-/-) mice and was not inhibited by the soluble β-glucan antagonist laminarin. In contrast, a much lower percentage of peritoneal macrophages from C3(-/-) mice phagocytosed GPs, and this percentage was further reduced in the presence of laminarin. Subcutaneous immunization of wild-type, Dectin-1(-/-), and C3(-/-) mice with GP-OVA resulted in similar Ag-specific IgG(1) and IgG(2c) type Ab and CD4(+) T cell lymphoproliferative responses. Moreover, while CD4(+) Th1 and Th2 responses measured by ELISPOT assay were similar in the three mouse strains, Th17 responses were reduced in C3(-/-) mice. Thus, although Dectin-1 is necessary for optimal phagocytosis of GPs in the absence of complement, complement dominates when both an intact complement system and Dectin-1 are present. In addition, Th-skewing after GP-based immunization was altered in C3(-/-) mice.
Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Haibin
H
Huang
Gary R
GR
Ostroff
Chrono K
CK
Lee
Sarika
S
Agarwal
Sanjay
S
Ram
Peter A
PA
Rice
Charles A
CA
Specht
Stuart M
SM
Levitz
D000818:Animals; D019138:Antibodies, Blocking / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003176:Complement C3 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D008024:Ligands; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D047071:beta-Glucans / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D000099181:Dectin-1
D019138:Antibodies, Blocking; D003176:Complement C3; D037181:Lectins, C-Type; D008024:Ligands; D010047:Ovalbumin; D047071:beta-Glucans; D000099181:Dectin-1