The role of TLR2 in vivo following challenge with Staphylococcus aureus and prototypic ligands

被引:70
作者
Mullaly, Sarah C. [1 ]
Kubes, Paul [1 ]
机构
[1] Univ Calgary, Dept Physiol & Biophys, Immunol Res Grp, Inst Infect Immun & Inflammat, Calgary, AB T2N 4N1, Canada
关键词
D O I
10.4049/jimmunol.177.11.8154
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Based on a wealth of in vitro macrophage studies, immunity to Staphylococcus aureus cell wall-derived peptidoglycan (PGN) and lipoteichoic acid has been attributed to TLR2. We investigated, whether the in vitro paradigm of TLR2 dominance would hold true in vivo. Using an experimental peritonitis model, we challenged mice, with PGN or lipoteichoic acid and found that only PGN resulted in significant leukocyte (primarily neutrophil) accumulation in the peritoneum at 4 h. PGN-mediated leukocyte recruitment was P-/E-selectin dependent but only partially TLR2 dependent, and also involved the C5aR. Concomitant inhibition of TLR2 and C5aR resulted in. a further reduction in PGN-induced peritonitis. Peritoneal neutrophilia was partially mast cell dependent; however, the defect could not be reconstituted. With TLR2(-/-) or C5aR(-/-) mast cells. Interestingly, macrophage-deficient mice did not have defective neutrophil recruitment. By 24 h, the response to PGN involved primarily monocytes and was TLR2 and C5aR independent. Finally, we challenged mice with live S. aureus and found a similar degree of TLR2 involvement in leukocyte recruitment to that observed with PGN. Most importantly, bacterial clearance from the spleen and peritoneum was not altered in TLR2(-/-) mice vs wild-type mice. Morbidity was only significantly increased in S. aureus-infected mice treated with a blocking Fab against C5aR. Taken together, these studies indicate that in vivo responses to prototypic TLR2 ligands do not necessarily recapitulate the absolute necessity for TLR2 observed in vitro, and additional receptors contribute; in. a significant manner, to PGN and S. aureus-mediated immune responses.
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页码:8154 / 8163
页数:10
相关论文
共 48 条
[1]   Mechanisms of phagocytosis in macrophages [J].
Aderem, A ;
Underhill, DM .
ANNUAL REVIEW OF IMMUNOLOGY, 1999, 17 :593-623
[2]  
Ajuebor MN, 1999, J IMMUNOL, V162, P1685
[3]   Toll-like receptors: critical proteins linking innate and acquired immunity [J].
Akira, S ;
Takeda, K ;
Kaisho, T .
NATURE IMMUNOLOGY, 2001, 2 (08) :675-680
[4]   Toll-like receptor signalling [J].
Akira, S ;
Takeda, K .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (07) :499-511
[5]   Endothelium-derived toll-like receptor-4 is the key molecule in LPS-induced neutrophil sequestration into lungs [J].
Andonegui, G ;
Bonder, CS ;
Green, F ;
Mullaly, SC ;
Zbytnuik, L ;
Raharjo, E ;
Kubes, P .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (07) :1011-1020
[6]   Lipopolysaccharide-induced leukocyte-endothelial cell interactions: A role for CD14 versus toll-like receptor 4 within microvessels [J].
Andonegui, G ;
Goyert, SM ;
Kubes, P .
JOURNAL OF IMMUNOLOGY, 2002, 169 (04) :2111-2119
[7]   Cooperation of toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein:: Role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling [J].
Bulut, Y ;
Faure, E ;
Thomas, L ;
Equils, O ;
Arditi, M .
JOURNAL OF IMMUNOLOGY, 2001, 167 (02) :987-994
[8]   LEUKOCYTE-ENDOTHELIAL CELL RECOGNITION - 3 (OR MORE) STEPS TO SPECIFICITY AND DIVERSITY [J].
BUTCHER, EC .
CELL, 1991, 67 (06) :1033-1036
[9]   VLA-4 INTEGRIN CAN MEDIATE CD11 CD18-INDEPENDENT TRANSENDOTHELIAL MIGRATION OF HUMAN MONOCYTES [J].
CHULUYAN, HE ;
ISSEKUTZ, AC .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (06) :2768-2777
[10]   Staphylococcus aureus peptidoglycan is a Toll-like receptor 2 activator:: a reevaluation [J].
Dziarski, R ;
Gupta, D .
INFECTION AND IMMUNITY, 2005, 73 (08) :5212-5216