Control of primary mouse cytomegalovirus infection in lung nodular inflammatory foci by cooperation of interferon-gamma expressing CD4 and CD8 T cells

PLoS Pathogens
Yvonne LuederReinhold Förster

Abstract

Human cytomegalovirus (CMV) and mouse cytomegalovirus (MCMV) infection share many characteristics. Therefore infection of mice with MCMV is an important tool to understand immune responses and to design vaccines and therapies for patients at the risk of severe CMV disease. In this study, we investigated the immune response in the lungs following acute infection with MCMV. We used multi-color fluorescence microscopy to visualize single infected and immune cells in nodular inflammatory foci (NIFs) that formed around infected cells in the lungs. These NIFs consisted mainly of myeloid cells, T cells, and some NK cells. We found that the formation of NIFs was essential to reduce the number of infected cells in the lung tissue, showing that NIFs were sites of infection as well as sites of immune response. Comparing mice deficient for several leukocyte subsets, we identified T cells to be of prime importance for restricting MCMV infection in the lung. Moreover, T cells had to be present in NIFs in high numbers, and CD4 as well as CD8 T cells supported each other to efficiently control virus spread. Additionally, we investigated the effects of perforin and interferon-gamma (IFNγ) on the virus infection and found important roles for bot...Continue Reading

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Citations

Jun 9, 2020·Frontiers in Cellular and Infection Microbiology·Eleanor Y LimMark R Wills
Aug 11, 2019·International Journal of Molecular Sciences·Luís Fonseca BritoFelix R Stahl
May 14, 2021·Microbiology and Molecular Biology Reviews : MMBR·Maelig G MorvanJay A Levy
Aug 6, 2021·Nature Communications·Ina Annelies StelzerPetra Clara Arck

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Methods Mentioned

BETA
FACS
PMA
Phenotyping
FCS
flow cytometry

Software Mentioned

AxioVision
ZEN blue
ImageJ

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