Abstract
The functions of Toll-like receptors (TLRs) 11–13 in central nervous system (CNS) infections are currently unknown. Using a murine model of neurocysticercosis, we investigated the expression and distribution of TLRs 11–13 by using both gene specific real-time PCR analysis and in situ immunofluoresence microscopy in both control and neurocysticercosis brains. In the mock infected brain, mRNAs of TLRs 11–13 were constitutively expressed. Parasite infection caused an increase of both mRNAs and protein levels of all three TLRs by several fold. All three TLR proteins were present in both CNS and immune cell types. Among them TLR13 was expressed the most in terms of number of positive cells and brain areas expressing it, followed by TLR11 and TLR12 respectively. Among the nervous tissue cells, TLRs 11–13 protein levels appeared highest in neurons. However, TLR13 expression was also present in ependymal cells, endothelial cells of pial blood vessels, and astrocytes. In contrast, infiltrating CD11b and CD11c positive myeloid cells predominantly produced TLR11 protein, particularly early during infection at 1 wk post infection (~50% cells). TLRs 12 and 13 proteins were present on approximately 5% of infiltrating immune cells. The infiltrating cells positive for TLRs 11–13 were mostly of myeloid origin, CD11b+ cells. This report provides a comprehensive analysis of the expression of TLRs 11–13 in normal and parasite infected mouse brains and suggests a role for them in CNS infections.
Highlights
Neurocysticercosis (NCC) is the most common parasitic disease of the central nervous system (CNS) caused by the larvae of Taenia solium [1]
Constitutive mRNA expression was present for each Toll-like receptors (TLRs) with a relatively
Among TLRs 11–13, expression of TLR13 was the highest in both normal and parasitic infected brains and remained at an elevated level throughout infection (Fig. 1). These results indicate that TLR 11– 13 mRNAs are expressed in normal, uninfected mouse brains and their levels of expression increase during parasite infection
Summary
Neurocysticercosis (NCC) is the most common parasitic disease of the central nervous system (CNS) caused by the larvae of Taenia solium [1]. This disease is a public health problem in many third world and developing countries [1,2,3]. The symptomatic phase of the disease includes clinical signs such as epilepsy [2], increased intracranial (i.c.) pressure, obstructive hydroencephalus, stroke, and encephalitis [1,4]. Autopsy specimens of symptomatic patients reveal evidence of inflammation consisting of a chronic granulomatous reaction [4]. Considering the CNS is devoid of a classically defined lymphatic system, the innate immune response might play a major role in this process
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