Abstract
Leprosy is an infectious disease that remains endemic in approximately 100 developing countries, where about 200,000 new cases are diagnosed each year. Moreover, multibacillary leprosy, the most contagious form of the disease, has been detected at continuously higher rates among Brazilian elderly people. Due to the so-called immunosenescence, characterized by several alterations in the quality of the immune response during aging, this group is more susceptible to infectious diseases. In view of such data, the purpose of our work was to investigate if age-related alterations in the immune response could influence the pathogenesis of leprosy. As such, we studied 87 individuals, 62 newly diagnosed and untreated leprosy patients distributed according to the age range and to the clinical forms of the disease and 25 healthy volunteers, who were studied as controls. The frequency of senescent and memory CD8+ leukocytes was assessed by immunofluorescence of biopsies from cutaneous lesions, while the serum levels of IgG anti-CMV antibodies were analyzed by chemiluminescence and the gene expression of T cell receptors' inhibitors by RT-qPCR. We noted an accumulation of memory CD8+ T lymphocytes, as well as reduced CD8+CD28+ cell expression in skin lesions from elderly patients, when compared to younger people. Alterations in LAG3 and PDCD1 gene expression in cutaneous lesions of young MB patients were also observed, when compared to elderly patients. Such data suggest that the age-related alterations of T lymphocyte subsets can facilitate the onset of leprosy in elderly patients, not to mention other chronic inflammatory diseases.
Highlights
Leprosy is a neglected chronic infectious disease caused by Mycobacterium leprae, which remains a public health problem in low-income countries [1, 2]
The aging process leads to a myriad of innate and adaptive immune system adaptations, which result in increased susceptibility to infections, reduction in vaccine response, and even greater incidence of cancer [35]
These alterations are related to T cell mediated immune response, the mechanisms by which they increase susceptibility to infectious diseases remain unknown [36]
Summary
Leprosy is a neglected chronic infectious disease caused by Mycobacterium leprae, which remains a public health problem in low-income countries [1, 2]. Leprosy presents a wide spectrum of clinical forms, which is essentially determined by the presence (or absence) of cellmediated immunity (CMI) against the pathogen. According to the Ridley and Jopling classification [7], tuberculoid forms (TLep) are characterized by a strong immune response to localized disease with a single (or few) skin lesion(s) without bacilli detection. Lepromatous forms (L-Lep) are characterized by several disseminated skin lesions with many bacilli, and the absence of CMI against M. leprae. Between these polar forms (TT and LL) there are borderline forms (BT, BB, and BL), which comprise most of the patients. There is a WHO classification, a more practical and operational classification, which classifies leprosy patients into two groups: paucibacillary leprosy (PB leprosy) that presents five or less skin lesions and no apparent bacilli in slit-skin smears; and multibacillary leprosy (MB leprosy) with more than five skin lesions [8]
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