The induction of a type 1 immune response following a Trypanosoma brucei infection is MyD88 dependent

被引:107
作者
Drennan, MB
Stijlemans, B
Van Den Abbeele, J
Quesniaux, VJ
Barkhuizen, M
Brombacher, F
De Baetselier, P
Ryffel, B
Magez, S
机构
[1] Vrije Univ Brussels VIB, Dept Cellular & Mol Interact, Lab Cellular & Mol Immunol, Brussels, Belgium
[2] CNRS, F-45071 Orleans, France
[3] Inst Trop Med, Unit Entomol, B-2000 Antwerp, Belgium
[4] Univ Cape Town, Immunol Infect Dis Med Res Council, Inst Infect Dis & Mol Med, Fac Hlth Sci,Univ Cape Town Unit, ZA-7925 Cape Town, South Africa
基金
英国惠康基金;
关键词
D O I
10.4049/jimmunol.175.4.2501
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The initial host response toward the extracellular parasite Trypanosoma brucei is characterized by the early release of inflammatory mediators associated with a type 1 immune response. In this study, we show that this inflammatory response is dependent on activation of the innate immune system mediated by the adaptor molecule MyD88. In the present study, MyD88-deficient macrophages are nonresponsive toward both soluble variant-specific surface glycoprotein (VSG), as well as membrane-bound VSG purified from T. brucei. Infection of MyD88-deficient mice with either clonal or nonclonal stocks of T. brucei resulted in elevated levels of parasitemia. This was accompanied by reduced plasma IFN-gamma and TNF levels during the initial stage of infection, followed by moderately lower VSG-specific IgG2a Ab titers during the chronic stages of infection. Analysis of several TLR-deficient mice revealed a partial requirement for TLR9 in the production of IFN-gamma and VSG-specific IgG2a Ab levels during T. brucei infections. These results implicate the mammalian TLR family and MyD88 signaling in the innate immune recognition of T. brucei.
引用
收藏
页码:2501 / 2509
页数:9
相关论文
共 58 条
[1]   Plasmodium berghei infection in mice induces liver injury by an IL-12-and toll-like receptor/myeloid differentiation factor 88-dependent mechanism [J].
Adachi, K ;
Tsutsui, H ;
Kashiwamura, S ;
Seki, E ;
Nakano, H ;
Takeuchi, O ;
Takeda, K ;
Okumura, K ;
Van Kaer, L ;
Okamura, H ;
Akira, S ;
Nakanishi, K .
JOURNAL OF IMMUNOLOGY, 2001, 167 (10) :5928-5934
[2]   Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function [J].
Adachi, O ;
Kawai, T ;
Takeda, K ;
Matsumoto, M ;
Tsutsui, H ;
Sakagami, M ;
Nakanishi, K ;
Akira, S .
IMMUNITY, 1998, 9 (01) :143-150
[3]   Lipopolysaccharide interaction with cell surface toll-like receptor 4-MD-2: Higher affinity than that with MD-2 or CD14 [J].
Akashi, S ;
Saitoh, S ;
Wakabayashi, Y ;
Kikuchi, T ;
Takamura, N ;
Nagai, Y ;
Kusumoto, Y ;
Fukase, K ;
Kusumoto, S ;
Adachi, Y ;
Kosugi, A ;
Miyake, K .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (07) :1035-1042
[4]   Toll-like receptors: critical proteins linking innate and acquired immunity [J].
Akira, S ;
Takeda, K ;
Kaisho, T .
NATURE IMMUNOLOGY, 2001, 2 (08) :675-680
[5]   Toll-like receptor signalling [J].
Akira, S ;
Takeda, K .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (07) :499-511
[6]   CCR5 provides a signal for microbial induced production of IL-12 by CD8α+ dendritic cells [J].
Aliberti, J ;
Sousa, CRE ;
Schito, M ;
Hieny, S ;
Wells, T ;
Huffnagle, GB ;
Sher, A .
NATURE IMMUNOLOGY, 2000, 1 (01) :83-87
[7]   PARASITE DEVELOPMENT AND HOST RESPONSES DURING THE ESTABLISHMENT OF TRYPANOSOMA-BRUCEI INFECTION TRANSMITTED BY TSETSE-FLY [J].
BARRY, JD ;
EMERY, DL .
PARASITOLOGY, 1984, 88 (FEB) :67-+
[8]   ANTIGENIC VARIATION IN AFRICAN TRYPANOSOMES [J].
BORST, P ;
RUDENKO, G .
SCIENCE, 1994, 264 (5167) :1872-1873
[9]   IL-12 is dispensable for innate and adaptive immunity against low doses of Listeria monocytogenes [J].
Brombacher, F ;
Dorfmüller, A ;
Magram, J ;
Dai, WJ ;
Köhler, G ;
Wunderlin, A ;
Palmer-Lehmann, K ;
Gately, MK ;
Alber, G .
INTERNATIONAL IMMUNOLOGY, 1999, 11 (03) :325-332
[10]   Impaired production of proinflammatory cytokines and host resistance to acute infection with Trypanosoma cruzi in mice lacking functional myeloid differentiation factor 88 [J].
Campos, MA ;
Closel, M ;
Valente, EP ;
Cardoso, JE ;
Akira, S ;
Alvarez-Leite, JI ;
Ropert, C ;
Gazzinelli, RT .
JOURNAL OF IMMUNOLOGY, 2004, 172 (03) :1711-1718