Marginal zone macrophages expressing SIGN-R1 are specifically recognized by the MAb ERTR9 [21, 34]

Marginal zone macrophages expressing SIGN-R1 are specifically recognized by the MAb ERTR9 [21, 34]. deposited in marginal zone macrophages. However, GXM deposition was found in the red pulp. These results indicate that there is a selective localization of these polysaccharides to different receptors such as SIGN-R1 for FITC dextran in marginal zone and a to-be-identified receptor selectively expressed by red pulp macrophages for GXM. is unusual among eukaryotic microbes because it contains a polysaccharide capsule with functional similarities to those of encapsulated bacteria such as, and [4, 5]. In fact, cryptococcal polysaccharide is known to share some antigenic determinants with certain pneumococcal polysaccharides [6, 7]. The capsule is composed of glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoprotein (MP), of which the major component on a mass basis is GXM [8, 9]. GXM can interfere with many aspects of immune function, including leukocyte migration and phagocytosis [3, 10C12]. The ability for GXM to interfere with immune function is believed to contribute to virulence by allowing the fungal cells to evade the immune system [11, 13]. GXM is also attributed to causing immunological paralysis, reducing the number of antibody producing Rabbit polyclonal to PC cells in the spleen [10]. The spleen is intimately involved with the effective clearance of pathogens by the immune system [14, 15]. The major compartments of the spleen are the JNJ-10397049 white and red pulp which are separated by the marginal zone (MZ) The MZ contains highly phagocytic macrophages that play a critical role in the spleen since it is the location where antigens that come into the marginal sinuses from the bloodstream are initially screened [16, 17]. Marginal zone macrophages (MZM) also have been found to exclusively uptake neutral polysaccharides such as Dextrans and Ficoll [16, 18]. In contrast, acidic polysaccharides localize primarily to the red pulp of the spleen [15, 16, 19]. The efficiency of this filtering system also results from the vascular structure of the red pulp through which blood is slowed down, enabling macrophages to phagocytose polysaccharide antigens [20]. The C-type lectin SIGN-related 1 (SIGN-R1) receptor is expressed on the macrophages of the marginal zone of the spleen and on medullary and subcapsular macrophages in lymph nodes [4, 21, 22]. SIGN-R1 is a mouse homologue of the DC-SIGN receptor found in dendritic cells. DC-SIGN is functionally associated with several, critically important biological processes including the ability to be hijacked by the HIV-1 virus, presentation and facilitating transmission of the virus to CD4+ T-cells [14, 21]. Recently it has been shown that SIGN-R1 can bind the complement C1 component C1q and assemble a C3 convertase against infection [23]. Furthermore, the SIGN-R1 receptor in the marginal zone macrophages can bind and internalize the capsular polysaccharide of and Dextrans [4, 22]. This phenomenon was demonstrated by using a transient SIGN-R1 receptor knock out system (TKO), whereby the monoclonal antibody (mAb) 22D1 is used to selectively block receptor function [4, 21, 23]. Several studies of GXM sequestration and tissue localization revealed that although JNJ-10397049 GXM is rapidly cleared from the circulation with a half life of 1 1.1C2.7 days this is then followed by a plateau with little elimination [24]. Intravenous administration of GXM in rats leads to the deposition in tissue macrophages [24]. However little is known about the mechanism by which GXM binds to macrophages or the fate of bound GXM [24]. In rats, GXM JNJ-10397049 was found to localize to the outer areas of the marginal zone by 5 hours after (i.v.) injection [1, 3]. GXM deposition in the spleen is accompanied by a rapid and intense burst of cytokine and chemokine expression [3, 24] Multiple receptors such as CD18, TLR4, CD14 and FCRII may be involved in the cellular uptake of GXM [25C27]. Since the SIGN-R1 receptor binds the.