Secretion of CXC chemokines by macrophages links TLR2-dependent sensing of Trypanosoma cruzi to mechanisms that steer innate immunity via bradykinin receptors (2006)
- USP affiliated authors: ALMEIDA, IGOR CORREIA DE - ICB
- USP Schools: ICB
- Subjects: PARASITOLOGIA
- Language: Inglês
- Abstract: Introduction and objectives: Plasma extravasation is a common endothelium response to tissue injury provoked by pathogens. Recently, we developed a subcutaneous model of T. cruzi (Dm28c) infection to study the role of the kinin system in immunity. First, we showed that tissue culture trypomastigotes (TCT) evoke edematogenic inflammation by activating the kinin system through mechanisms that involve cooperative signaling of TLR2 and the B2-bradykinin receptor (B2R). Analysis of the early stages of inflammation revealed that TCT activate neutrophils/endothelium in a TLR2 dependent manner. Owing to disruption of endothelial barrier function, the levels of blood-borne kininogens (i.e. kinin precursor proteins) are rapidly raised in infection sites. Once associated to extracellular matrix, kininogens are processed by parasite proteases (i.e., cruzipain), generating high-levels of bradykinin in peripheral tissues. Acting as maturation signals for dendritic cells, the short-lived kinins steer adaptive immunity via the B2R/Il-12 dependent pathway.Methods and results: In the present study, we studied how the presence of this pathogen is sensed by immune sentinel cells. Analysis of TCT interaction with bone marrow derived mast cells (BMMCs) showed that mast cells do not degranulate (?-hexosaminidase secretion). In contrast, measurements of secretion of CXC chemokines revealed that mouse macrophages (WT, TLR4def, B2R-/-, resident or TG-elicited)vigorously responded to TCT. Notably, TLR2-/- macrophages did not secrete appreciable amounts of KC or MIP-2, neither responded to tGPI-mucin (TLR2 ligand) stimuli. Consistent with these results, epimastigotes and metacyclic trypomastigotes, both of which fail to evoke inflammatory responses in vivo, did not induce CXC chemokine secretion in macrophages. Addition of ACE inhibitors mildly up regulated secretion of KC/MIP-2 and the effect was blocked by the B2R antagonist. Conclusion: Collectively, our studies suggest that secretion of CXC chemokines secretion by macrophages, a TLR2-dependent response, sets in motion an inflammatory cascade that steers innate immunity through DCs via the bradykinin signaling pathway.
- Título do periódico: Abstracts
- Conference titles: Meeting of the Brazilian Society for Immunology
ABNTSCHMITZ, V; ANDRADE, D S; ALMEIDA, Igor Correia de; DIAZ, B L; SCHARFTEIN, J. Secretion of CXC chemokines by macrophages links TLR2-dependent sensing of Trypanosoma cruzi to mechanisms that steer innate immunity via bradykinin receptors. Anais.. São Paulo: [s.n.], 2006.
APASchmitz, V., Andrade, D. S., Almeida, I. C. de, Diaz, B. L., & Scharftein, J. (2006). Secretion of CXC chemokines by macrophages links TLR2-dependent sensing of Trypanosoma cruzi to mechanisms that steer innate immunity via bradykinin receptors. In Abstracts. São Paulo.
NLMSchmitz V, Andrade DS, Almeida IC de, Diaz BL, Scharftein J. Secretion of CXC chemokines by macrophages links TLR2-dependent sensing of Trypanosoma cruzi to mechanisms that steer innate immunity via bradykinin receptors. Abstracts. 2006 ;
VancouverSchmitz V, Andrade DS, Almeida IC de, Diaz BL, Scharftein J. Secretion of CXC chemokines by macrophages links TLR2-dependent sensing of Trypanosoma cruzi to mechanisms that steer innate immunity via bradykinin receptors. Abstracts. 2006 ;
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