IL-12Rβ2 Is Essential for the Development of Experimental Cerebral Malaria

被引：37

作者：

Fauconnier, Mathilde ^{[2
]}

Palomo, Jennifer ^{[2
]}

Bourigault, Marie-Laure ^{[2
]}

Meme, Sandra ^{[3
]}

Szeremeta, Frederic ^{[3
]}

Beloeil, Jean-Claude ^{[3
]}

Danneels, Adeline ^{[2
]}

Charron, Sabine ^{[2
]}

Rihet, Pascal ^{[4
,6
]}

Ryffel, Bernhard ^{[2
,5
]}

Quesniaux, Valerie F. J. ^{[1
,2
]}

机构：

[1] CNRS, Transgenose Inst, Unite Mixte Rech Ex UMR6218 7355, F-45071 Orleans, France

[2] Univ Orleans, Unite Mixte Rech 6218, F-45071 Orleans, France

[3] CNRS, Ctr Biophys Mol, F-45071 Orleans, France

[4] INSERM, Unite Mixte Rech 928, F-13288 Marseille, France

[5] Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa

[6] Aix Marseille Univ, F-13288 Marseille, France

来源：

JOURNAL OF IMMUNOLOGY | 2012年 / 188卷 / 04期

关键词：

PLASMODIUM-BERGHEI INFECTION; NECROSIS-FACTOR-ALPHA; LYMPHOTOXIN-ALPHA; IFN-GAMMA; T-CELLS; PROTECTIVE IMMUNITY; IMAGING FINDINGS; PATHOGENIC ROLE; MICE; INTERLEUKIN-12;

D O I：

10.4049/jimmunol.1101978

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

A Th1 response is required for the development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM). The role of pro-Th1 IL-12 in malaria is complex and controversial. In this study, we addressed the role of IL-12R beta 2 in ECM development. C57BL/6 mice deficient for IL-12R beta 2, IL-12p40, or IL-12p35 were analyzed for ECM development after blood-stage PbA infection in terms of ischemia and blood flow by noninvasive magnetic resonance imaging and angiography, T cell recruitment, and gene expression. Without IL-12R beta 2, no neurologic sign of ECM developed upon PbA infection. Although wildtype mice developed distinct brain microvascular pathology, ECM-resistant, IL-12R beta 2-deficient mice showed unaltered cerebral microcirculation and the absence of ischemia after PbA infection. In contrast, mice deficient for IL-12p40 or IL-12p35 were sensitive to ECM development. The resistance of IL-12R beta 2-deficient mice to ECM correlated with reduced recruitment of activated T cells and impaired overexpression of lymphotoxin-alpha, TNF-alpha, and IFN-gamma in the brain after PbA infection. Therefore, IL-12R beta 2 signaling is essential for ECM development but independent from IL-12p40 and IL-12p35. We document a novel link between IL-12R beta 2 and lymphotoxin-alpha, TNF-alpha, and IFN-gamma expression, key cytokines for ECM pathogenesis. The Journal of Immunology, 2012, 188: 1905-1914.

引用

页码：1905 / 1914

页数：10

共 52 条

[31] Multiple sclerosis: The proinflammatory cytokines lymphotoxin-alpha and tumour necrosis factor-alpha are upregulated in cerebrospinal fluid mononuclear cells [J].

Matusevicius, D ;

Navikas, V ;

Soderstrom, M ;

Xiao, BG ;

Haglund, M ;

Fredrikson, S ;

Link, H .

JOURNAL OF NEUROIMMUNOLOGY, 1996, 66 (1-2) :115-123

[32] A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production [J].

Morahan, G ;

Boutlis, CS ;

Huang, D ;

Pain, A ;

Saunders, JR ;

Hobbs, MR ;

Granger, DL ;

Weinberg, JB ;

Peshu, N ;

Mwaikambo, ED ;

Marsh, K ;

Roberts, DJ ;

Anstey, NM .

GENES AND IMMUNITY, 2002, 3 (07) :414-418

[33] Perforin-dependent brain-infiltrating cytotoxic CD8+ T lymphocytes mediate experimental cerebral malaria pathogenesis [J].

Nitcheu, J ;

Bonduelle, O ;

Combadiere, C ;

Tefit, M ;

Seilhean, D ;

Mazier, D ;

Combadiere, B .

JOURNAL OF IMMUNOLOGY, 2003, 170 (04) :2221-2228

[34]

Normaznah Y, 1999, Malays J Pathol, V21, P123

[35] Adult cerebral malaria: Prognostic importance of imaging findings and correlation with postmortem findings [J].

Patankar, TF ;

Karnad, DR ;

Shetty, PG ;

Desai, AP ;

Prasad, SR .

RADIOLOGY, 2002, 224 (03) :811-816

[36] Imaging experimental cerebral malaria in vivo:: Significant role of ischemic brain edema [J].

Penet, MF ;

Viola, A ;

Confort-Gouny, S ;

Le Fur, Y ;

Duhamel, G ;

Kober, F ;

Ibarrola, D ;

Izquierdo, M ;

Coltel, N ;

Gharib, B ;

Grau, GE ;

Cozzone, PJ .

JOURNAL OF NEUROSCIENCE, 2005, 25 (32) :7352-7358

[37] Pathogenic T cells in cerebral malaria [J].

Renia, Laurent ;

Potter, Sarah M. ;

Mauduit, Marjorie ;

Rosa, Daniela Santoro ;

Kayibanda, Michle ;

Deschemin, Jean-Christophe ;

Snounou, Georges ;

Gruner, Anne Charlotte .

INTERNATIONAL JOURNAL FOR PARASITOLOGY, 2006, 36 (05) :547-554

[38] IL-12p40-independent induction of protective immunity upon multiple Plasmodium berghei irradiated sporozoite immunizations [J].

Romero, J. F. ;

Ibrahim, G. H. ;

Renggli, J. ;

Himmelrich, H. ;

Graber, P. ;

Corradin, G. .

PARASITE IMMUNOLOGY, 2007, 29 (11) :541-548

[39]

Rudin W, 1997, AM J PATHOL, V150, P257

[40] Immunological processes in malaria pathogenesis [J].

Schofield, L ;

Grau, GE .

NATURE REVIEWS IMMUNOLOGY, 2005, 5 (09) :722-735

← 1 2 3 4 5 6 →