Presence of Senescent and Memory CD8+ Leukocytes as Immunocenescence Markers in Skin Lesions of Elderly Leprosy Patients

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.

The immune-suppressive landscape in lepromatous leprosy revealed by single-cell RNA sequencing

“…Similarly, the expression of LAG3 , another exhaustion marker, was also reported to be elevated in T cells infected by various viruses, such as herpes simplex virus 1, human immunodeficiency virus, and lymphocytic choriomeningitis virus 45 – 47 . And an increased expression of LAG3 in lesions of multibacillary leprosy compared to paucibacillary leprosy was also reported recently 48 . Nevertheless, to the best of our knowledge, little is known about the roles of TIGIT in chronic bacterial infection.…”

Immunosenescence and Skin: A State of Art of Its Etiopathogenetic Role and Crucial Watershed for Systemic Implications

“…However, this etiologic influence can be mitigated by the good maintenance of flagellin-dependent TLR5 signaling in senescent macrophages, which is subsidiary to caveolin-1's immunoactivating action [168]. More recently, the etiopathogenetic influence of immunosenescence has also been recognized for active tuberculosis and leprosy with reference to monocyte phenotypic changes and age-related rearrangement of T lymphocyte subsets, respectively [169,170].…”