Evidence of Involvement of the Mannose Receptor in Adhesion ofBorrelia burgdorferito Monocyte/Macrophages

Abstract

The mannose receptor (MR) plays an important role in the recognition of some pathogens in nonopsonic phagocytosis and in antigen presentation to T cells. We found that Borrelia burgdorferi, the agent of Lyme borreliosis, adheres to monocyte-derived macrophages and to rat MR-transfected cells but not to untransfected cells. Antibodies to MR and sugars such as mannose, mannan, fucose, and some lectins significantly lowered the adhesion, confirming participation of the MR in the binding.The etiological agent of Lyme disease, Borrelia burgdorferi, is able to disseminate widely and avoid clearance by innate immunity and by the immune system, thereby establishing chronic infection. Spirochetes undertake complex interactions with a variety of mammalian cells, which contribute to the establishment of infection in the host. Such interactions consist of adhesion to cells and tissues: B. burgdorferi binds to platelets via the integrins ␣ II ␤ 3 and to endothelial cells through the integrins ␣ V ␤ 3 and ␣ 5 ␤ 1 (7,8) and to a variety of cells which express glycosaminoglycans such as heparin, heparan sulfate, and dermatan sulfate (19, 2). Lyme borreliosis Borrelia also recognizes other substrates like fibronectin (17, 23) and decorins (12), which explains the attachment of B. burgdorferi to the extracellular matrix of the skin and other tissues. Binding to such receptors as integrins, which are true cell-associated receptors, not only provides adhesion to cells, allowing B. burgdorferi to attach itself firmly to the tissues, but also can induce effector mechanisms, normally triggered by the integrin under appropriate stimuli. This is the case with integrin ␣ M ␤ 2 , a dynamic molecule also known as CR3 or CD11b/CD18 receptor; this molecule was shown to bind borrelias (4) and trigger phagocytosis by neutrophils in the absence of specific opsonization; such binding activates the molecule to up-regulation and increases adhesion to fibronectin (6). The binding seems to involve not only the I domain of the molecule, specific for the iC3b and the RGD motif, but also the lectin-like domain, which is known to recognize lipopolysaccharide, mannose, and other sugar residues (5).Another cell receptor which is involved in microbe recognition and phagocytosis in the absence of specific opsonization is the mannose receptor (MR), which acts as a true lectin in the lectin phagocytosis of microorganisms (22). It is a type I transmembrane glycoprotein of 165 kDa containing as many as eight adjoining carbohydrate recognition domains, a fibronectin type II domain, and a cysteine-rich domain (2); it is expressed on tissue macrophages, dendritic cells (mostly on Langerhans cells), endothelium, and rat microglia. Besides acting as a scavenger of mannose-containing glycoconjugates on the surface of a wide spectrum of microorganisms, such as Escherichia coli, Klebsiella pneumoniae, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Candida albicans, Leishmania, and Pneumocystis carinii (21), it mediates their ingestion by macrophages. Moreover, it ...

Phagocytic Receptors Activate Syk and Src Signaling during Borrelia burgdorferi Phagocytosis

“…pathogen (11,(35)(36)(37). Interestingly, ␣M␤2 was required for the attachment of the bacterium to the host cell but not for its internalization (13,14).…”

Lyme Arthritis: Current Concepts and a Change in Paradigm

“…In addition, interaction of macrophages with borrelial antigens induces the production of proinflammatory mediators such as nitric oxide, IL-1, TNF-␣, IL-6, and IL-12 (97), as well as mediators of tissue destruction such as matrix metalloproteinase 9 (MMP-9) (162). Moreover, the spread of B. burgdorferi is hindered by the ability of macrophages and dendritic cells to readily bind and phagocytize B. burgdorferi by a variety of means (36,53,91,(103)(104)(105)107). These findings demonstrate that the presence of B. burgdorferi in the skin upon initial infection establishes a rapid, robust innate response by monocytes, macrophages, and dendritic cells in an attempt to stem the dissemination of spirochetes.…”

Optimal T Cell Responses to Cryptococcus neoformans Mannoprotein Are Dependent on Recognition of Conjugated Carbohydrates by Mannose Receptors

“…The MMR can recognize patterns of exposed hexoses, including mannose and fucose, but not galactose (26). The MMR can interact with a range of mannose-decorated whole pathogens and Ags, including Borrelia burgdorferi (30) and lipoarabinomannans from pathogenic mycobacteria (31)(32)(33). We hypothesized that APCs, which express MMR and DEC-205, target cryptococcal MP for receptor-mediated uptake and subsequent efficient Ag presentation to T cells.…”