These analyses were done using GraphPad Prism 3
These analyses were done using GraphPad Prism 3.03 software package (San Diego, CA, USA). CD14 monocytes were represented by dogs without parasite ear tissue load that were unable to infect phlebotomines (IHQ/XENO). Dogs with lower expression of MFI of CD11b inside CD14 monocytes were represented by dogs with parasite ear tissue load and able to infect phlebotomines (IHQ+/XENO+) (p = 0,0032). Comparable results were obtained for MFI of MHCII (p = 0.0054). In addition, considering the population frequency of CD11b+TLR2+and CD11b+MHCII+, higher values were obtained from dogs with IHQ/XENOthan dogs with IHQ+/XENO+(p = 0.01; p = 0.0048, respectively). These data, together with the TLR2 and NO assays results (CD11b+TLR2+and NO with higher values for dogs with IHQ/XENOthan dogs with IHQ+/XENO+), led to the conclusion that IHQ/XENOdogs are more resistant or could modulate the cellular immune response essential forLeishmaniatissue clearance. == Introduction == Toll-like receptors (TLRs) function as pathogen recognition receptors (PRRs) that recruit GSK-3787 active signaling molecules involved in innate immunity[1]. These receptors located on the plasma membrane or internal membranes of macrophages, dendritic cells (DCs), NK cells and T and B lymphocytes, recognize pathogen-associated molecular patterns (PAMPs) such as glycolipids, peptidoglycans and lipopeptides, which are produced only by microorganisms and not by host cells[2]. After this recognition there is a spectrum of regulatory inflammatory MGC33310 cytokines production by the host. Evidences that TLRs are important microbial sensors came from models of infection in TLR-deficient mice. In addition, reported polymorphisms in certain TLRs and signaling adaptors predict susceptibility to infectious diseases[3]. A total of 11 human and 13 mouse TLRs have been identified and each responds to distinct PAMPs, leading to the activation of specific signaling pathways. Among TLRs located on internal membranes, TLR3, TLR7, TLR8 and TLR9 have been described and TLR1, TLR2, GSK-3787 TLR4, TLR5 and TLR6 are located on plasma membranes[4]. The majority of work concerning TLRs has involved bacterial and fungal pathogens, but some studies have suggested that they may play a role in GSK-3787 recognizing protozoan parasites beyond glycosylphosphatidylinositol (GPI) anchors and glycoinositol phospholipids (GIPL)[5].Leishmaniacell surfaces are dominated by GPI-anchored and GPI-related molecules and abundant GIPLs that are not attached to a protein and tend to form dense layers on the parasite surface, above other GPI-anchored molecules such as lipophosphoglycan (LPG)[6]. It has been demonstrated that LPG inL. majoractivates cells of the innate immune response through TLR-2. Therefore, owing GSK-3787 to its structural characteristics and its GPI anchor, LPG represents aLeishmanialigand for TLRs[7],[8]. The study carried out by Hawn et al. (2002)[9]was the first to evaluate TLRs inLeishmaniainfection. The authors demonstrated that there was less IL-1alfa mRNA expression in MyD88 (intracellular signaling protein) knockout mice. However, this study evaluatedin vitrocytokine promoter (adaptor protein MyD88) and not TLR activation. Following this work, de Veer et al. 2003 and Beker et al. (2003)[7],[8]demonstrated that LPG was associated with an increase in TNF- levels after NF-kB activation by TLR2, suggesting that three molecules of LPG could aggregate with one molecule of TLR2. Therefore, these studies appear to invalidate the concept of the unresponsiveness of TLR2 in leishmaniasis[10]. Several non-TLR receptor chains including CD14, MHC class II and the integrin-like CD11b/CD18 receptors (CR3 – complement receptor type 3) cooperate with TLRs in recognizing PAMPs[11]. Therefore, the aim of this study was to investigate the expression of TLR2 in peripheral blood monocytes cells of symptomatic dogs naturally infected withLeishmania (L.) infantum (syn:L. chagasi)[12]and its correlation with CR3 expression. Moreover, skin.