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Cutting Edge: TLR9 and TLR2 Signaling Together Account for MyD88-Dependent Control of Parasitemia in Trypanosoma cruzi Infection
Open accessAbstract
Activation of innate immune cells by Trypanosoma cruzi-derived molecules such as GPI anchors and DNA induces proinflammatory cytokine production and host defense mechanisms. In this study, we demonstrate that DNA from T. cruzi stimulates cytokine production by APCs in a TLR9-dependent manner and synergizes with parasite-derived GPI anchor, a TLR2 agonist, in the induction of cytokines by macrophages. Compared with wild-type animals, T. cruzi-infected Tlr9−/− mice displayed elevated parasitemia and decreased survival. Strikingly, infected Tlr2−/−Tlr9−/− mice developed a parasitemia equivalent to animals lacking MyD88, an essential signaling molecule for most TLR, but did not show the acute mortality displayed by MyD88−/− animals. The enhanced susceptibility of Tlr9−/− and Tlr2−/−Tlr9−/− mice was associated with decreased in vivo IL-12/IFN-γ responses. Our results reveal that TLR2 and TLR9 cooperate in the control of parasite replication and that TLR9 has a primary role in the MyD88-dependent induction of IL-12/IFN-γ synthesis during infection with T. cruzi.
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Cites
Takeda, K., Kaisho, T., & Akira, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141126 · Cited by 6,143
Bafica, A., Scanga, C. A., Feng, C. G., Leifer, C., Cheever, A., & Sher, A. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051782 · Cited by 601
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David Sibley, L. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00990.x · Cited by 254
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Błyszczuk, P. (2019) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2019.00064 · Cited by 161
Gonçalves, V. M., Matteucci, K. C., Buzzo, C. L., Miollo, B. H., Ferrante, D., Torrecilhas, A. C., Rodrigues, M. M., Alvarez, J. M., & Bortoluci, K. R. (2013) · PLoS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0002469 · Cited by 123
Metadata
- Authors
- Bafica, A., Santiago, H. C., Goldszmid, R., Ropert, C., Gazzinelli, R. T., & Sher, A.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-09
- Volume
- 177
- Issue
- 6
- Pages
- 3515-3519
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2160660031
- Cited by
- 296
- References
- 2
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Bafica, A., Santiago, H. C., Goldszmid, R., Ropert, C., Gazzinelli, R. T., & Sher, A. (2006). Cutting Edge: TLR9 and TLR2 Signaling Together Account for MyD88-Dependent Control of Parasitemia in Trypanosoma cruzi Infection. The Journal of Immunology. https://doi.org/10.4049/jimmunol.177.6.3515
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