Abstract
Pathogenic mycobacteria species may subvert the innate immune mechanisms and can modulate the activation of cells that cause disease in the skin. Cutaneous mycobacterial infection may present different clinical presentations and it is associated with stigma, deformity, and disability. The understanding of the immunopathogenic mechanisms related to mycobacterial infection in human skin is of pivotal importance to identify targets for new therapeutic strategies. The occurrence of reactional episodes and relapse in leprosy patients, the emergence of resistant mycobacteria strains, and the absence of effective drugs to treat mycobacterial cutaneous infection increased the interest in the development of therapies based on repurposed drugs against mycobacteria. The mechanism of action of many of these therapies evaluated is linked to the activation of autophagy. Autophagy is an evolutionary conserved lysosomal degradation pathway that has been associated with the control of the mycobacterial bacillary load. Here, we review the role of autophagy in the pathogenesis of cutaneous mycobacterial infection and discuss the perspectives of autophagy as a target for drug development and repurposing against cutaneous mycobacterial infection.
Highlights
Pathogenic mycobacteria species subvert the innate immune system barriers and modulate the activation of phagocytes to cause disease in the respiratory tract and in soft tissues and skin, sometimes resulting in disseminated infection [1]
Initial studies that evaluated the effect of verapamil and its analogs on macrophages infected with M. tuberculosis showed that the structural analog KSV21 had an additive effect on the inhibitory antimicrobial activity of Isoniazid and Rifampicin [143]
This review describes the potential of host cell autophagy as a target for the development of new strategies against mycobacterial diseases
Summary
Pathogenic mycobacteria species subvert the innate immune system barriers and modulate the activation of phagocytes to cause disease in the respiratory tract and in soft tissues and skin, sometimes resulting in disseminated infection [1]. After recognition by skin cells, mycobacteria may use a wide range of strategies to escape the microbicidal activity of skin host cells Some of these immune escape mechanisms are the inhibition of the maturation of phagolysosomes, inhibition of the acidification of phagolysosomes, bacterial escape to reside in the cytosol, modulation of host cell metabolism, inhibition of oxidative stress, and inhibition of apoptosis and autophagy associated with increased type 1 interferon (IFN) expression and inflammasome activation [16,17,18,19,20,21,22,23]. We discuss the current knowledge of, advances and perspectives on new therapeutic strategies targeting autophagy against mycobacterial infections in the skin
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