Studies into the mechanism of measles-associated immune suppression during a measles outbreak in the Netherlands

Brigitta M Laksono,Pieter L A Fraaij,Menno C Van Zelm,Eline G Visser,Alwin De Jong,Henk-Jan Van Den Ham,Rory D De Vries,Rik L De Swart,Albert D M E Osterhaus,R Joyce Verburgh,Wilhemina L M Ruijs,Marion P G Koopmans,David F Nieuwenhuijse

doi:10.1038/s41467-018-07515-0

Abstract

Measles causes a transient immune suppression, leading to increased susceptibility to opportunistic infections. In experimentally infected non-human primates (NHPs) measles virus (MV) infects and depletes pre-existing memory lymphocytes, causing immune amnesia. A measles outbreak in the Dutch Orthodox Protestant community provided a unique opportunity to study the pathogenesis of measles immune suppression in unvaccinated children. In peripheral blood mononuclear cells (PBMC) of prodromal measles patients, we detected MV-infected memory CD4+ and CD8+ T cells and naive and memory B cells at similar levels as those observed in NHPs. In paired PBMC collected before and after measles we found reduced frequencies of circulating memory B cells and increased frequencies of regulatory T cells and transitional B cells after measles. These data support our immune amnesia hypothesis and offer an explanation for the previously observed long-term effects of measles on host resistance. This study emphasises the importance of maintaining high measles vaccination coverage.

Highlights

Measles causes a transient immune suppression, leading to increased susceptibility to opportunistic infections
In experimentally infected non-human primates (NHPs), measles virus (MV) initially targets myeloid cells in the respiratory tract, which act as Trojan horses by transmitting MV to CD150+ lymphocytes in lymphoid tissues, leading to viraemia and systemic virus dissemination[12,13,14,15]
MV infection causes cell-associated viraemia, and the virus was isolated from peripheral blood mononuclear cells (PBMC) obtained from 22 out of 23 patients (Fig. 1d)

Summary

Introduction

Measles causes a transient immune suppression, leading to increased susceptibility to opportunistic infections. In experimentally infected non-human primates (NHPs) measles virus (MV) infects and depletes pre-existing memory lymphocytes, causing immune amnesia. We hypothesised that MV causes immunological amnesia by infecting and depleting pre-existing memory lymphocytes[17,20] Consistent with this hypothesis, a subsequent epidemiological study found that rates of non-measles infectious disease mortality are tightly coupled to measles incidence—with a greater mortality rate at higher recent measles incidence. In 2013, a measles outbreak occurred largely among the Orthodox Protestant community that refuses vaccination on religious grounds, with more than 2600 cases reported[23] This outbreak presented us with a unique opportunity to study the pathogenesis of measlesassociated immune suppression in natural measles patients. We show that measles causes significant changes in the frequency of circulating lymphocyte subsets, which are still detectable more than a month after recovery

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Results

Conclusion