In situTLR2 and TLR4 expression in a murine model of mycetoma caused byNocardia brasiliensis

Abstract

Actinomycetoma caused by Nocardia brasiliensis is a common disease in tropical regions. This ailment is characterized by a localized chronic inflammation that mainly affects the lower limbs. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns, inducing the production of proinflammatory mediators. The role of TLRs in the immune response against N. brasiliensis is unknown. The aim of this work was to locate and quantify in a murine model the expression of TLR2 and TLR4 in the infection site using reverse transcription-PCR and immunohistochemistry. The results showed that TLR2 expression increased in the infected tissue, whereas TLR4 expression decreased. The presence of TLR2 and TLR4 was demonstrated in different cell populations throughout the chronic infectious process. In the early stages of this process, TLR2 was expressed in neutrophils and macrophages in direct contact with the inoculum, whereas TLR4 was observed in mast cells. In the advanced stages of the infection, TLR2 was expressed in foam cells and fibroblasts and was likely associated with bacterial containment, while TLR4 was downregulated, probably resulting in an imbalance between the host immune response and the bacterial load that favoured chronic disease.

Nocardia farcinica Activates Human Dendritic Cells and Induces Secretion of Interleukin-23 (IL-23) Rather than IL-12p70

“…DCs might become activated through the interaction of nocardial antigens with the extracellular receptor TLR2, which is expressed by monocyte-derived human DCs (31) and has previously been shown to also recognize antigenic structures derived from the cell wall of N. coeliaca (51). Increased TLR2 expression has also been observed in inflammatory lesions of murine mycetoma caused by N. brasiliensis (41). TLR2 is known to bind a large variety of ligands from Gram-positive and Gram-negative bacteria, but also from parasites and fungi (2).…”

Eumycetoma and actinomycetoma – an update on causative agents, epidemiology, pathogenesis, diagnostics and therapy

“…Millán‐Chiu et al . investigated the in situ Toll‐like receptor (TLR) expression in a murine model of mycetoma due to Nocardia brasiliensis .…”

“…Mill an-Chiu et al 39 investigated the in situ Toll-like receptor (TLR) expression in a murine model of mycetoma due to Nocardia brasiliensis. They were able to demonstrate that TLR2 expression increased in the infected tissue, whereas TLR4 expression decreased.…”

Stimulation of the Protective Response to Actinomycetoma by <i>Nocardia brasiliensis</i> in Mice Treated with <i>Candida albicans</i> Antigens

“…Bacterial components of N. brasiliensis are recognized as MAMPs by TLRs that have a role in resolution of the infection given that their unbalanced expression induces the persistence of the actinomycetoma [18].…”