Mechanismof interferon- -mediated anti-chlamydia infection
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1 Journal of Microbes and Infection, June 2009, Vol. 4, No ,,, :,,, ; : ; ; ; Mechanismof interferon- -mediated anti-chlamydia infection TANG Guo-Fang, LI Zhong-Yu, WU Yi-Mou Institute of Pathogenic Biology Institute, School of Medicine, University of South China, Hengyang , China Abstract: Chlamydia is an intracellular bacterium that infects many vertebrates, including humans. Previous studies have shown that interferon- ( IFN- ) plays an important role in defense against Chlamydia infection. IFN- - mediated anti-chlamydia effector mechanisms may include the exhaustion of tryptophan, the induction of iron loss, and/ or the activation of inducible nitric oxide synthase ( inos). However, Chlamydia has evolved to develop mechanisms to escape IFN- functions. In this review, we will discuss IFN- -mediated effector mechanisms in the control of Chlamydia infection. Key words:chlamydia; Interferon- ; Immune response; Immune escape,,, ( Chlamydia trachomatic, Ct),,, 10% ( Chlamydia pneumoniae, Cpn), Cpn,,,, CD4 + : ( ) :, yimouwu@ sina. com. cn Th1 [ 1], Th1 ( interferon Corresponding author: WU Yi-Mou, yimouwu@ sina. com. cn, IFN- ) [ 2 ], IFN- 1 IFN- IFN-, ( Chlamydia muridarum),, IFN- IFN- / IFN- R / ( IFN- IFN- ),2 100% [ 3 ] IFN- ; IFN-,, ( reticulate body, RB), RB, IFN-, RB,, ( elementary body, EB)
2 Journal of Microbes and Infection, June 2009, Vol. 4, No. 2 IFN-, Ct IFN-, IFN- [ 4] IFN- 2 IFN- CD8 + T CD4 + T ( natural killer, NK) - IFN-, IFN-, 2. 1 IFN- 1,, NK,, [ 5] Toll ( Toll-like receptor, TLR) ( heat shock protein60, HSP 60), IFN-, [ 6, 7 ] ( severe combined immunodeficiency, SCID), IFN- RAG-1 / / IFN- R / SCID ; 1 ( recombination activating gene 1, RAG-1) T B, IFN- SCID < RAG-1 / SCID, [ 8 ], IFN- NK NK T IFN-, IFN- NK, NK [ 5, 7, 9], NK, RAG- 1 / NK,, ; RAG- 1 / cr / ( B T NK / ) Cpn IFN- RAG-1 IFN- [ 10 ] NK T, IFN- Cpn J 18 ( NK T CD1d ), NK T Cpn NK T Cpn,,, Cpn NK T, NK T1, IFN-,, Cpn ; NK T2, 4 ( interleukin4, IL-4),, [ 11] NK T [ 12 ] NK NK T, IFN- Cpn ( bone-marrowderived macrophages, BMM) IFN- mrna [ 13 ] RAG- 1 / / IFN- /, Cpn, IFN-, [ 14] 2. 2 IFN-,,, [ 15 ], CD8 + T CD4 + T [ 1], CD8 + CD4 + T,,, IFN-, Ct DNA T IFN-, Ct DNA IFN- R /, Cpn DNA [ 16, 17 ], IFN- CD4 + Th1 Ct, Ct IFN- ( major histocompatibility complex, MHC), CD4 + T, IFN- CD4 + T, CD4 + T IFN- Ct, [ 18] IFN- /,, T
3 Journal of Microbes and Infection, June 2009, Vol. 4, No [ 19], IFN-, Ct L2 ( Chlamydial protease-like activity factor, CPAF) Th1 CpG IFN- / IFN- R /, CPAF CD4 + T IFN- R /, IFN-, ;, CPAF CD4 + T IFN- /, IFN-,, CD4 + IFN- [ 20], MHC CD4 + T T, IFN- Ct DNA Ct, CD8 + T, CD8 + T, [ 21] CD8 + Cpn ; T ( major outer membrane protein, MOMP) <,, Fas/FasL Cpn [ 21 ] ; CD8 + T, CD8 + T,, IFN- [ 21], CD8 + T IFN- Cpn, CrpA ( cysteine-rich membrane protein A) OmcB ( 60 kd cysteine-rich outer membrane protein B) CD8 + T IFN-, Ct [ 22, 23 ], Ct Tvinnereim [ 24], MHCIb H2-M3 Cpn P1 P4, CD8 + T IFN-, Cpn CD8 + T Kb - / - /Db - / -, Cpn, CD8 + T IFN-, Cpn T IFN-, IFN- / T IFN-, IFN- ;,,,, 3 IFN- IFN-, IFN- IFN- 2,3 ( indoleamine 2, 3-dioxygenase, IDO) ( inducible nitric oxide synthase, inos) ; IFN- IDO, ( nitrogen monoxide, NO) ; NO, IDO [ 25 ] Ct, IFN- p47 GTPase ( GTPases IRGs, ), Ct [ 18, 26] 3. 1 IFN- IDO IDO, IFN- IDO, L- N-,,, IFN- trpa trpb trpr trpc Cpn Ct,,, ( lipopolysaccharide, LPS) IL-1 ( tumor necrosis factor, TNF) IFN-IDO 3. 2 IFN- inos IFN- inos, L- NO, inos /,, inos / IFN- R / ;, Roshick [ 25 ], IFN- ( McCoy L929 RAW J774) NO, NO Ct
4 Journal of Microbes and Infection, June 2009, Vol. 4, No. 2, IFN- inos, IFN- IFN- NADPHgp IFN-,,, [ 27] IFN-, : IFN- ( transferrin receptor, TFR), [ 28] ; IFN- - ( ferroportin),, [ 28] ; IFN- - 1( divalent metal transporter 1, DMT1), -, [ 28 ], IFN- ( hepcidin), Paradkar [ 29], Ct ( Chlamydia psittaci, Cps), -,, IFN- 4 IFN- IFN-, IFN-, Ct > 99%,, IFN- Ct,, Ct IFN-p47 GTPases, Irgm1( Lrg47) Irgm3( Igtp) Irgb10 Irga6, GTPases Irgb10, IFN- [ 30], ( plasticity zone, PZ) IFN-, PZ IFN- PZ 3 ( TC437 TC439), clcts cyopt : clcts UDP-, GTPases ; cyopt GTPases, IFN- p47 GTPase [ 3 1] IFN- IDO,,, IFN-, -1 ( upstream stimulatory factor-1, USF-1), IFN-, IFN- MHC, CD4 + T [ 3 2] 5,,,, ;, IFN-, CD4 + T CD8 + T IFN-, CD4 + T CD8 + T IFN- [ 1] Roan NR, Starnbach MN. Immune-mediated control of Chlamydia infection[ J]. Cell Microbiol, 2008, 10( 1) : 9-19 [ 2] Brunham RC, Rey-Ladino J. Immunology of Chlamydia infection: implications for a Chlamydia trachomatis vaccine[ J]. Nat Rev Immunol, 2005, 5( 2) : [ 3] Jupelli M, Guentzel MN, Meier PA, et al. Endogenous IFN-gamma production is induced and required for protective immunity against pulmonary chlamydial infection in neonatal mice[ J]. J Immunol, 2008, 180 ( 6) : [ 4] Morrison RP, Caldwell HD. Immunity to murine chlamydial genital infection[ J]. Infect Immun, 2002, 70 ( 6) : [ 5] Wira CR, Fahey JV, Sentman CL, et al. Innate and adaptive immunity in female genital tract: cellular responses and interactions [ J]. Immunol Rev, 2005, 206:
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