Abstract
This study continues to explore the plasticity of Toll-like receptor 2 (TLR2) previously described in immune response during Trypanosoma cruzi infection. Here, we have shown that Ly6ChiTLR2hi monocytes were involved in TNF-α and IL-12 production, whereas Ly6CloTLR2hi monocytes were mainly committed to IL-10 and TNF-α production during T. cruzi infection independently of TLR agonist used (i.e. TLR2 or TLR9 agonists). Another difference between the monocyte populations is that the adapter Mal (encoded by TIRAP) has appeared crucial for the cytokine production by Ly6Clo but not by Ly6Chi monocytes. The protein Mal was necessary to induce cytokine synthesis by Ly6Clo monocytes after triggering TLR2 or TLR9. Finally, our data have suggested that TLR2, TLR9, and Mal/TIRAP controlled differentially the emergence of the different TLR2hi monocyte populations in the spleen. In summary, this study highlights the central role of the TLR2/Mal tandem in the distinct activity among the monocyte subsets during T. cruzi infection. Such findings provide a basis for understanding the challenge posed by the use of TLR2 agonist in immunotherapy.
Highlights
TLRs2 play a critical role in the innate immunity by recognizing the pathogen-associated molecular patterns, which may be expressed differentially according to the cell type [1, 2]
To have a comprehensive overview of the functional consequence of Toll-like receptor 2 (TLR2) activation during T. cruzi infection, we have focused on monocytes that express TLR2
TLR2 appears to play a dual role during T. cruzi infection inducing a pro-inflammatory response in macrophage but controlling TLR9-dependent IL-12 production by DCs [5, 12]
Summary
Characterization of Two Splenic Monocyte Populations Expressing High Levels of TLR2 during the Acute Phase of T. cruzi Infection—We sought to define different splenic subpopulations of monocytes by using TLR2 as a marker. We verified that Ly6ChiTLR2hi and Ly6CloTLR2hi populations were producers of cytokines (e.g. TNF-␣) when stimulated with Pam3Cys, a TLR2 agonist The Role of TLR2 and TLR9 in the Modulation of Splenic TLR2hi Monocyte Number during T. cruzi Infection—As previously described, the evolution of the number of Ly6ChiTLR2hi and Ly6CloTLR2hi splenic cells was different during infection. An increase of the number of Ly6ChiTLR2hi monocytes has been observed in spleen cell culture from infected and non-infected mice in the presence of TLR agonists, indicating they may influence the Ly6Chi population. The data are representative of three independent experiments (means Ϯ S.D. of four animals)
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