Role of Toll-like receptors in patients with multiple sclerosis and Chlamydophila pneumoniae infection

Objectives: The possibility that Multiple Sclerosis (MS) is linked to chronic infection by Chlamydophila pneumoniae (Cpn) has attracted attention in these last years. Previous studies have demonstrated that in a subset of MS patients with Relapsing-Remitting (RR) forms, Cpn could induce a chronic persistent brain infection acting as a cofactor in the development of the disease. Moreover, mRNA transcript levels of Cpn 16sRNA and HsP60 genes, have been detected in PBMC and CSF compared to other neurological disorders (OND) patients found Reverse Transcriptase (RT) PCR positive for 1 gene only. Literature evidence has established that there is a high expression of Toll like receptors (TLR) in various neurodegenerative disorders including SM (active lesions of microglia and astrocytes). We have evaluated the link between Cpn and the molecular expression of TLRs by studying clinical specimens from MS patients infected by Cpn before and after co-culture on Hep-2 cells specific for this pathogen. Methods: Fresh CSF and PBMC specimens were obtained from 20 patients with SM RR and 19 controls with OND previously investigated for Cpn 16 s rRNA and Hsp60 genes by PCR and RT-PCR. TLR2 and TLR4 expression was studied by RT-PCR in clinical specimens before and after inoculation and incubation in CO2 for 144 h, on Hep-2 cells. Results: An evident expression for either TLR2 or TLR4 receptors (9/10, 90%; 7/10, 70%, respectively) was found in patients with SM RR before PBMC but not CSF culture inoculation. These patients have shown to highly express TLR-2 and TLR-4 (6/10; 60%), in contrast with OND patients who were found to express TLR2 (2/10; 20%) or TLR4 (1/10; 10%7) but not both. Conclusions: TLRs are transmembrane pattern-recognition receptors that initiate signals in response to diverse pathogen-associated molecular patterns. The major expression of TLR-2 and TLR-4 in peripheral blood and not in CSF from SM patients and particularly those with RR forms, indicate that their combined activity might be crucial to modulate and activate cellular-mediated immune response during chronic infections by Chlamydia. In fact, MS patients show immunological and cytokine elevations consistent with chronic infection