TLR2 synergizes with both TLR4 and TLR9 for induction of the MyD88-dependent splenic cytokine and chemokine response to Streptococcus pneumoniae.
We previously demonstrated that induction of splenic cytokine and chemokine secretion in response to Streptococcus pneumoniae (Pn) is MyD88-, but not critically TLR2-dependent, suggesting a role for additional TLRs. In this study, we investigated the role of TLR2, TLR4, and/or TLR9 in mediating this response. We show that a single deficiency in TLR2, TLR4, or TLR9 has only modest, selective effects on cytokine and chemokine secretion, whereas substantial defects were observed in TLR2(-/-)xTLR9(-/-) and TLR2(-/-)xTLR4(-/-) mice, though not as severe as in MyD88(-/-) mice. Chloroquine, which inhibits the function of intracellular TLRs, including TLR9, completely abrogated detectable cytokine and chemokine release in spleen cells from TLR2(-/-)xTLR4(-/-) mice, similar to what is observed for mice deficient in MyD88. These data demonstrate significant synergy between TLR2 and both TLR4 and TLR9 for induction of the MyD88-dependent splenic cytokine and chemokine response to Pn.
Lee
Katherine S
KS
Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
Scanga
Charles A
CA
Bachelder
Eric M
EM
Chen
Quanyi
Q
Snapper
Clifford M
CM
D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D003433:Crosses, Genetic; D016207:Cytokines / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D011008:Pneumococcal Infections / Q000276:immunology*; D040081:Protein Array Analysis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000502:physiology; D051193:Toll-Like Receptors / Q000235:genetics / Q000502:physiology*
D018925:Chemokines; D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors