CCR5 is essential for NK cell trafficking and host survival following Toxoplasma gondii infection

被引:136
作者
Khan, Imtiaz A.
Thomas, Seddon Y.
Moretto, Magali M.
Lee, Frederick S.
Islam, Sabina A.
Combe, Crescent
Schwartzman, Joseph D.
Luster, Andrew D.
机构
[1] Department of Microbiology, Immunology, and Parasitology, Louisiana State University Medical Center, New Orleans, LA
[2] Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
[3] Department of Pathology, Dartmouth Medical School, Lebanon, NH
关键词
D O I
10.1371/journal.ppat.0020049
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The host response to intracellular pathogens requires the coordinated action of both the innate and acquired immune systems. Chemokines play a critical role in the trafficking of immune cells and transitioning an innate immune response into an acquired response. We analyzed the host response of mice deficient in the chemokine receptor CCR5 following infection with the intracellular protozoan parasite Toxoplasma gondii. We found that CCR5 controls recruitment of natural killer (NK) cells into infected tissues. Without this influx of NK cells, tissues from CCR5-deficient (CCR5(-/-)) mice were less able to generate an inflammatory response, had decreased chemokine and interferon c production, and had higher parasite burden. As a result, CCR5(-/-) mice were more susceptible to infection with T. gondii but were less susceptible to the immune-mediated tissue injury seen in certain inbred strains. Adoptive transfer of CCR5(-/-) NK cells into CCR5(-/-) mice restored their ability to survive lethal T. gondii infection and demonstrated that CCR5 is required for NK cell homing into infected liver and spleen. This study establishes CCR5 as a critical receptor guiding NK cell trafficking in host defense.
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页码:484 / 500
页数:17
相关论文
共 55 条
[1]   CDNA CLONING AND INTERFERON-GAMMA DOWN-REGULATION OF PROTEASOMAL SUBUNIT-X AND SUBUNIT-Y [J].
AKIYAMA, KY ;
YOKOTA, KY ;
KAGAWA, S ;
SHIMBARA, N ;
TAMURA, T ;
AKIOKA, H ;
NOTHWANG, HG ;
NODA, C ;
TANAKA, K ;
ICHIHARA, A .
SCIENCE, 1994, 265 (5176) :1231-1234
[2]   Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells [J].
Alberti, J ;
Valenzuela, JG ;
Carruthers, VB ;
Hieny, S ;
Andersen, J ;
Charest, H ;
Sousa, CRE ;
Fairlamb, A ;
Ribeiro, JM ;
Sher, A .
NATURE IMMUNOLOGY, 2003, 4 (05) :485-490
[3]   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
[4]   Mice with a selective deletion of the CC chemokine receptors 5 or 2 are protected from dextran sodium sulfate-mediated colitis:: Lack of CC chemokine receptor 5 expression results in a NK1.1+ lymphocyte-associated Th2-type immune response in the intestine [J].
Andres, PG ;
Beck, PL ;
Mizoguchi, E ;
Mizoguchi, A ;
Bhan, AK ;
Dawson, T ;
Kuziel, WA ;
Maeda, N ;
MacDermott, RP ;
Podolsky, DK ;
Reinecker, HC .
JOURNAL OF IMMUNOLOGY, 2000, 164 (12) :6303-6312
[5]   Cutting edge:: The mouse NK cell-associated antigen recognized by DX5 moncoclonal antibody is CD49b (α2 integrin, very late antigen-2) [J].
Arase, H ;
Saito, T ;
Phillips, JH ;
Lanier, LL .
JOURNAL OF IMMUNOLOGY, 2001, 167 (03) :1141-1144
[6]   CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis [J].
Barcellos, LF ;
Schito, AM ;
Rimmler, JB ;
Vittinghoff, E ;
Shih, A ;
Lincoln, R ;
Callier, S ;
Elkins, MK ;
Goodkin, DE ;
Haines, JL ;
Pericak-Vance, MA ;
Hauser, SL ;
Oksenberg, JR .
IMMUNOGENETICS, 2000, 51 (4-5) :281-288
[7]   The CCR5 deletion mutation fails to protect against multiple sclerosis [J].
Bennetts, BH ;
Teutsch, SM ;
Buhler, MM ;
Heard, RNS ;
Stewart, GJ .
HUMAN IMMUNOLOGY, 1997, 58 (01) :52-59
[8]   Rapid recruitment of neutrophils containing prestored IL-12 during microbial infection [J].
Bliss, SK ;
Butcher, BA ;
Denkers, EY .
JOURNAL OF IMMUNOLOGY, 2000, 165 (08) :4515-4521
[9]   Cellular responses to interferon-gamma [J].
Boehm, U ;
Klamp, T ;
Groot, M ;
Howard, JC .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :749-795
[10]   DIRECT AND SENSITIVE DETECTION OF A PATHOGENIC PROTOZOAN, TOXOPLASMA-GONDII, BY POLYMERASE CHAIN-REACTION [J].
BURG, JL ;
GROVER, CM ;
POULETTY, P ;
BOOTHROYD, JC .
JOURNAL OF CLINICAL MICROBIOLOGY, 1989, 27 (08) :1787-1792