Interleukin-4- and NACHT, LRR and PYD domains-containing protein 3-independent mechanisms of alum enhanced T helper type 2 responses on basophils.
Aluminium hydroxide (alum), the most widely used adjuvant in human and animal vaccines, has long been known to promote T helper type 2 (Th2) responses and Th2-associated humoral responses, but the mechanisms have remained poorly understood. In this study, we explored whether alum is able to directly modulate antigen-presenting cells to enhance their potency for Th2 polarization. We found that alum treatment of dendritic cells failed to show any Th2-promoting activities. In contrast, alum was able to enhance the capacity of basophils to induce Th2 cells. When basophils from interleukin-4 (IL-4) knockout mice were examined, the intrinsic Th2-promoting activities by basophils were largely abrogated, but the alum-enhanced Th2-promoting activities on basophils were still detectable. More importantly, Th2-promoting adjuvant activities by alum found in IL-4 knockout mice were also largely reduced when basophils were depleted by antibody administration. Therefore, basophils can mediate Th2-promoting activities by alum both in vitro and in vivo through IL-4-independent mechanisms. Further studies revealed that secreted soluble molecules from alum-treated basophils were able to confer the Th2-promoting activities, and neutralization of thymic stromal lymphopoietin or IL-25 attenuated the IL-4-independent development of Th2 cells elicited by alum-treated basophils. Finally, alum was able to activate NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in murine basophils in the same way as alum in professional antigen-presenting cells, but NLRP3 was not required for Th2-promoting activities on basophils by alum in vitro. These results demonstrated that alum can enhance the capacities of basophils to polarize Th2 cells via IL-4- and NLRP3-independent pathways.
Department of Immunology and Pathogen Biology, TongJi University School of Medicine, Shanghai, China.
Feng-Juan
FJ
Huang
Department of Immunology and Pathogen Biology, TongJi University School of Medicine, Shanghai, China.
Yi-Lei
YL
Ma
Department of Immunology and Pathogen Biology, TongJi University School of Medicine, Shanghai, China.
Ruo-Yu
RY
Tang
Department of Immunology and Pathogen Biology, TongJi University School of Medicine, Shanghai, China.
Wen-Ci
WC
Gong
Department of Immunology and Pathogen Biology, TongJi University School of Medicine, Shanghai, China.
Jun
J
Li
Department of Immunology and Pathogen Biology, TongJi University School of Medicine, Shanghai, China.
Chun-Xia
CX
Chen
Department of Immunology and Pathogen Biology, TongJi University School of Medicine, Shanghai, China.
Lan
L
Yin
Department of Immunology and Pathogen Biology, TongJi University School of Medicine, Shanghai, China.
Xiao-Ping
XP
Chen
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000534:Alum Compounds / Q000008:administration & dosage*; D000818:Animals; D017951:Antigen Presentation; D001491:Basophils / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D014612:Vaccines; D015847:Interleukin-4; C041524:aluminum sulfate
NACHT, LRR and PYD domains-containing protein 3; T helper type 2 response; aluminium hydroxide; basophils; interleukin-4