The immune status of Kupffer cells profoundly influences their responses to infectious Plasmodium berghei sporozoites.
Multi-factorial immune mechanisms underlie protection induced with radiation-attenuated Plasmodia sporozoites (gamma-spz). Spz pass through Kupffer cells (KC) before invading hepatocytes but the involvement of KC in protection is poorly understood. In this study we investigated whether gamma-spz-immune KC respond to infectious spz in a manner that is distinct from the response of naive KC to infectious spz. KC were isolated from (1) naive, (2) spz-infected, (3) gamma-spz-immune, and (4) gamma-spz-immune-challenged C57BL/6 mice and examined for the expression of MHC class I and II, CD40 and CD80/CD86, IL-10 and IL-12 responses and antigen-presenting cell (APC) function. KC from gamma-spz-immune-challenged mice up-regulated class I and costimulatory molecules and produced elevated IL-12p40, relative to naive KC. In contrast, KC from naive mice exposed to infectious spz down-modulated class I and IL-12p40 was undetectable. Accordingly, KC from spz-infected mice had reduced APC function, while KC from gamma-spz-immune-challenged mice exhibited augmented APC activity. The nearly opposite responses are consistent with the fact that spz challenge of gamma-spz-immune mice results in long-lasting sterile protection, while infection of naive mice always results in malaria.
Steers
Nick
N
Department of Immunology, WRAIR, Silver Spring, MD 20910, USA.
Schwenk
Robert
R
Bacon
David J
DJ
Berenzon
Dmitri
D
Williams
Jackie
J
Krzych
Urszula
U
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007728:Kupffer Cells / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008288:Malaria / Q000276:immunology* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000254:growth & development / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D034101:Sporozoites / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma