Measles skin rash: infection of lymphoid and myeloid cells in the dermis precedes viral dissemination to keratinocytes in the epidermis

Abstract

2 precedes viral dissemination to keratinocytes in the epidermis 3 4 The pathogenesis of measles skin rash 5 6 2 24 Abstract 25 Measles is characterised by fever and a maculopapular skin rash, which is associated with 26 immune clearance of measles virus (MV)-infected cells. Histopathological analyses of skin 27 biopsies from humans and non-human primates (NHPs) with measles rash have identified 28 MV-infected keratinocytes and mononuclear cells in the epidermis, around hair follicles and 29 near sebaceous glands. Here, we address the pathogenesis of measles skin rash by combining 30 data from experimentally infected NHPs, ex vivo infection of human skin sheets and in vitro 31 infection of primary human keratinocytes. Longitudinal analysis of the skin of experimentally32 MV-infected NHPs demonstrated that infection in the skin precedes onset of rash by several 33 days. MV infection was initiated in lymphoid and myeloid cells in the dermis before 34 dissemination to the epidermal keratinocytes. These data were in good concordance with ex 35 vivo MV infections of human skin sheets, in which dermal cells were more targeted than the 36 epidermal ones. To address viral dissemination to the epidermis and to determine whether 37 the dissemination is receptor-dependent, we performed experimental infections of primary 38 keratinocytes collected from healthy or nectin-4-deficient donors. These experiments 39 demonstrated that MV infection of keratinocytes is nectin-4-dependent, and nectin-4 40 expression was higher in differentiated than in proliferating keratinocytes. Based on these 41 data, we hypothesise that measles skin rash is initiated by migrating MV-infected 42 lymphocytes that infect dermal skin-resident CD150 + immune cells. The infection is 43 subsequently disseminated from the dermal papillae to nectin-4 + keratinocytes in the basal 44 epidermis. Lateral spread of MV infection is observed in the superficial epidermis, most likely 45 due to the higher level of nectin-4 expression on differentiated keratinocytes. Finally, MV-46 infected cells are cleared by infiltrating immune cells, causing hyperaemia and oedema, which 47 give the appearance of morbilliform skin rash.3 48 49 Author Summary 50 Several viral infections are associated with skin rash, including parvovirus B19, human 51 herpesvirus type 6, dengue virus and rubella virus. However, the archetype virus infection 52 that leads to skin rash is measles. Although all of these viral exanthemata often appear similar, 53 their pathogenesis is different. In the case of measles, the appearance of skin rash is a sign 54 that the immune system is clearing MV-infected cells from the skin. How the virus reaches 55 the skin and is locally disseminated remains unknown. Here we combine observations and 56 expertise from pathologists, dermatologists, virologists and immunologists to delineate the 57 pathogenesis of measles skin rash. We show that MV infection of dermal myeloid and 58 lymphoid cells precedes viral dissemination to the epidermal keratinocytes. We specula...

Immunity parameters in adults with measles compared with healthy persons

“…Оба эти цитокина оказались значимо повышены в группе больных корью. Воздействие вируса кори на эпителий и иммунную систему кожи является предметом серьезного изучения [19], однако нам не удалось найти исследования уровней этих цитокинов при кори в мировой литературе. Описанные выше данные, взятые вместе, свидетельствуют о том, что клетки эпителия активно участвуют в иммунном ответе на вирус кори.…”