Cerebral malaria in mice -: Interleukin-2 treatment induces accumulation of γδ T cells in the brain and alters resistant mice to susceptible-like phenotype

被引:22
作者
Haque, A
Echchannaoui, H
Seguin, R
Schwartzman, J
Kasper, LH
Haque, S
机构
[1] Univ Mediterranee, Fac Med, CNRS, INSERM,U399, F-13385 Marseille, France
[2] Dartmouth Med Sch, Dept Med & Microbiol, Lebanon, NH USA
[3] Dartmouth Med Sch, Dept Pathol, Lebanon, NH USA
关键词
D O I
10.1016/S0002-9440(10)63954-5
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
In this study, we report that infection with Plasmodium yoelii 17XL, a lethal strain of rodent malaria, does not result in death in the DBA/2 strain of mice. In contrast to BALB/c mice, DBA/2 mice developed significantly less parasitemia and never manifested symptoms of cerebral malaria (CM) on infection with this parasite. Moreover, the histological changes evident in the brain of susceptible BALB/c were absent in DBA/2 mice. Interestingly, the resistant DBA/2 mice when treated with recombinant interleukin (IL)-2, were found to develop CM symptoms and the infection became fatal by 6 to 8 days after infection. This condition was associated with an augmented interferon-gamma and nitric oxide production. Unexpectedly, IL-10 levels were also elevated in IL-2-treated DBA/2 mice during late stage of infection (at day 6 of infection) whereas the inverse relationship between IL-10 and interferon-gamma or nitric oxide was maintained in the early stage of infection (at day 3 after infection). The level of tumor necrosis factor-alpha production was moderately increased in the late phase of infection in these mice. Histology of brain from IL-2-treated mice demonstrated the presence of parasitized erythrocytes and infiltration of lymphocytes in cerebral vessels, and also displayed some signs of endothelial degeneration. Confocal microscopical studies demonstrated preferential accumulation of gamma delta T cells in the cerebral vessels of IL-2-treated and -infected mice but not in mice treated with IL-2 alone. The cells recruited in the brain were activated because they demonstrated expression of CD25 (IL-2R) and CD54 (intercellular adhesion molecule 1) molecules. Administration of anti-gamma delta mAb prevented development of CM in IL-2-treated mice until day 18 after infection whereas mice treated with control antibody showed CM symptoms by day 6 after infection. The information concerning creating pathological sequelae and death in an otherwise resistant mouse strain provides an interesting focus for the burden of pathological attributes on death in an infectious disease.
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页码:163 / 172
页数:10
相关论文
共 47 条
[1]   Association between serum levels of reactive nitrogen intermediates and coma in children with cerebral malaria in Papua New Guinea [J].
AlYaman, FM ;
Mokela, D ;
Genton, B ;
Rockett, KA ;
Alpers, MP ;
Clark, IA .
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1996, 90 (03) :270-273
[2]   Nitric oxide in Tanzanian children with malaria: Inverse relationship between malaria severity and nitric oxide production nitric oxide synthase type 2 expression [J].
Anstey, NM ;
Weinberg, JB ;
Hassanali, M ;
Mwaikambo, ED ;
Manyenga, D ;
Misukonis, MA ;
Arnelle, DR ;
Hollis, D ;
McDonald, MI ;
Granger, DL .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (02) :557-567
[3]   NITRIC-OXIDE - A PHYSIOLOGICAL MESSENGER MOLECULE [J].
BREDT, DS ;
SNYDER, SH .
ANNUAL REVIEW OF BIOCHEMISTRY, 1994, 63 :175-195
[4]  
Brown H, 1999, NEUROPATH APPL NEURO, V25, P331
[5]   LATE DOMINANCE OF THE INFLAMMATORY PROCESS IN MURINE INFLUENZA BY GAMMA-DELTA+ T-CELLS [J].
CARDING, SR ;
ALLAN, W ;
KYES, S ;
HAYDAY, A ;
BOTTOMLY, K ;
DOHERTY, PC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 172 (04) :1225-1231
[6]   EXPRESSION AND REGULATION OF ADHESION MOLECULES BY GAMMA-DELTA T-CELLS FROM LYMPHOID-TISSUES AND INTESTINAL EPITHELIUM [J].
CHAO, CC ;
SANDOR, M ;
DAILEY, MO .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1994, 24 (12) :3180-3187
[7]  
CHRISTMAS SE, 1990, IMMUNOLOGY, V71, P486
[8]   POSSIBLE CENTRAL ROLE OF NITRIC-OXIDE IN CONDITIONS CLINICALLY SIMILAR TO CEREBRAL MALARIA [J].
CLARK, IA ;
ROCKETT, KA ;
COWDEN, WB .
LANCET, 1992, 340 (8824) :894-896
[9]   INTERLEUKIN-10 (IL-10) INHIBITS THE INDUCTION OF NITRIC-OXIDE SYNTHASE BY INTERFERON-GAMMA IN MURINE MACROPHAGES [J].
CUNHA, FQ ;
MONCADA, S ;
LIEW, FY .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 182 (03) :1155-1159
[10]   PENTOXIFYLLINE AS A SUPPORTIVE AGENT IN THE TREATMENT OF CEREBRAL MALARIA IN CHILDREN [J].
DIPERRI, G ;
DIPERRI, IG ;
MONTEIRO, GB ;
BONORA, S ;
HENNIG, C ;
CASSATELLA, M ;
MICCIOLO, R ;
VENTO, S ;
DUSI, S ;
BASSETTI, D ;
CONCIA, E .
JOURNAL OF INFECTIOUS DISEASES, 1995, 171 (05) :1317-1322