Abstract
Mycetoma is a chronic infectious disease that can be caused by fungi or bacteria, Madurella mycetomatis and Nocardia brasiliensis are frequent etiologic agents of this disease. Mycetoma produced by bacteria is known as actinomycetoma. In mycetoma produced by fungi (eumycetoma) and actinomycetoma, diagnosis of the disease is based on clinical findings: severe inflammation, with deformities of affected tissues, abscesses, fistulae, sinuses and discharge of purulent material that contains micro colonies of the etiologic agent. Microscopic examination of infected tissue is similar regardless of the offending microbe; hallmark of infected tissue is severe inflammation with abundant neutrophils around micro colonies and granuloma formation with macrophages, lymphocytes, dendritic and foamy cells. Even though medical treatment is available for mycetoma patients, amputation, or surgical intervention is frequently needed. The pathogenesis of actinomycetoma is little known, most information was obtained from experimental animal models infected with bacteria. In other experimental mice infections with different microbes, it was demonstrated that nitric oxide is responsible for the intracellular killing of Mycobacterium tuberculosis by activated macrophages. Nitric oxide is a free radical with potent stimulatory and suppressive effects in innate and adaptive immunity. The unstable nitric oxide molecule is produced by action of nitric oxide synthases on L-arginine. There are three nitric oxide synthases expressed in different cells and tissues, two are constitutively expressed one in neurons, and the other in endothelial cells and one that is inducible in macrophages. Aminoguanidine is a competitive inhibitor of inducible nitric oxide synthase. Its administration in experimental animals may favor or harm them. We used aminoguanidine in mice infected with Nocardia brasiliensis, and demonstrated that all treated animals were protected from actinomycetoma development. Anti N. brasiliensis antibodies and T cell proliferation were not affected, but inflammation was reduced.
Highlights
Mycetoma is a chronic human infection produced by fungi or bacteria
Infectious disease produced by bacteria or fungi may be preventable through vaccination; there is no available vaccine for this and other infections
Aminoguanidine was given to experimental mice and it was found that this treatment, completely prevented inflammation and the mycetoma lesion
Summary
Mycetoma is a chronic human infection produced by fungi (eumycetoma) or bacteria (actinomycetoma) This disease causes a deforming inflammation of affected tissue, usually the extremities, and had been recently listed as a Neglected Tropical Disease [1]. We created an experimental actinomycetoma model in mice, with Nocardia brasiliensis ATCC700358 (formerly HUJEG-1) injected in the rear footpad, to study the host-parasite relationship [4]. This model has been useful to investigate the pathogenesis of actinomycetoma, since it reproduces the same macroscopic changes such as intense swelling with severe deformation of affected extremities. The hallmark of infected tissue in human and experimental mice is acute and chronic inflammation characterized by a large number of micro abscesses and granulomas, with foamy cells, macrophages, lymphocytes, and extensive fibrosis around the micro colonies of the bacteria or fungi
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