Expression of Toll-Like Receptor 2 on Human Schwann Cells: a Mechanism of Nerve Damage in Leprosy

Abstract

For patients with leprosy, nerve damage is a major cause of morbidity. Although antibiotic therapy can eliminate the pathogen, Mycobacterium leprae, therapy is often initiated after nerve damage has occurred. Furthermore, nerve damage can occur during the administration of therapy, in particular, during the reactive states of erythema nodosum leprosum and the reversal reaction.In all forms of leprosy, M. leprae can be detected in nerves in active lesions (24). The M. leprae-Schwann cell interaction is a complex process, involving multiple bacterial ligands and cellular receptors (21). One initial target for the M. leprae interaction with peripheral nerves is laminin 2, located in the basal lamina of the Schwann cell axon unit (22). A specific glycolipid of M. leprae has been shown to mediate this interaction and hence determine the predilection of M. leprae for nerves (17). Other mycobacteria, including M. tuberculosis, M. chelonae, and M. smegmatis, exhibit laminin-binding capacity for adherence to Schwann cells (14). The colonization of Schwann cells by M. leprae also stimulates granuloma formation and cellmediated nerve injury (28). However, damage to cutaneous nerves can also occur in the absence of immune cells (23). Therefore, study of the M. leprae-Schwann cell interaction is essential for understanding the mechanisms of nerve injury in leprosy.

A Dominant Role of Toll-Like Receptor 4 in the Signaling of Apoptosis in Bacteria-Faced Macrophages

“…The transient overexpression and activation of TLR2 mediated apoptosis in HEK293 cells, although to a lesser extent as compared with TLR4. Previous studies, that were reporting apoptosis through TLR2 stimulation, were conducted predominantly on human monocytic THP-1 cells, THP-1-derived macrophages, and human Schwann cells (12,47,60,61), while our experiments were done on mouse J774A.1 and primary peritoneal macrophages. This suggests that there may exist cell type-specific differences in TLR-responsive apoptosis signaling, which could be related to the distinct engagement of intracellular adapter proteins by TLR2 and TLR4.…”

Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis

“…Interestingly, the levels of TLR2 expression in the brain were reported to increase in response to peripheral challenge with either TLR2 or TLR4 bacterial ligands. Oliveira et al (43) have recently reported the presence of TLR2 on human Schwann cells. A prominent role for TLR4 in neuronal injury has been established by Vartanian and colleagues (44).…”

Morphological and functional characterizations of Schwann cells stimulated with Mycobacterium leprae

“…SC line culture -The ST88-14 tumor cell line, established from malignant Schwannomas (neurofibrosarcoma) of patients with NF-1 (Oliveira et al 2003), was generously donated by J. A. Fletchter (Dana Farber Cancer Institute, Boston, USA).…”

“…The resulting studies have shown that M. leprae can invade SC (Marques et al 2001b) by a specific laminin-binding protein of 21kDa (Marques et al 2001a) in addition to PGL-I . Furthermore, Oliveira et al (2003) have demonstrated the expression of Toll-like receptors within ST88-14 that can be activated by M. leprae lipoproteins and, consequently, lead to apoptosis and cytokine release by SC. More recently, the mannose receptor, which facilitates M. leprae entry into SC in this cell line, has been identified (Cruz 2006).…”