Programmed death-1 (PD-1)-deficient mice are extraordinarily sensitive to tuberculosis.

Proceedings of the National Academy of Sciences of the United States of America
Eszter Lázár-MolnárWilliam R Jacobs

Abstract

The programmed death-1 (PD-1) costimulatory receptor inhibits T and B cell responses and plays a crucial role in peripheral tolerance. PD-1 has recently been shown to inhibit T cell responses during chronic viral infections such as HIV. In this study, we examined the role of PD-1 in infection with Mycobacterium tuberculosis, a common co-infection with HIV. PD-1-deficient mice showed dramatically reduced survival compared with wild-type mice. The lungs of the PD-1-/- mice showed uncontrolled bacterial proliferation and focal necrotic areas with predominantly neutrophilic infiltrates, but a lower number of infiltrating T and B cells. Proinflammatory cytokines, such as TNF-alpha, IL-1, and especially IL-6 and IL-17 were significantly increased in the lung and sera of infected PD-1-/- mice, consistent with an aberrant inflammation. Microarray analysis of the lungs infected with M. tuberculosis showed dramatic differences between PD-1-/- and control mice. Using high-stringency analysis criteria (changes of twofold or greater), 367 transcripts of genes were differentially expressed between infected PD-1-/- and wild-type mice, resulting in profoundly altered inflammatory responses with implications for both innate and adaptive immunit...Continue Reading

References

Feb 27, 2001·Nature Immunology·Y LatchmanG J Freeman
Mar 13, 2001·Annual Review of Immunology·J L Flynn, J Chan
Nov 8, 2001·Proceedings of the National Academy of Sciences of the United States of America·T OkazakiT Honjo
Jul 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Philip SmithPadraic G Fallon
Dec 16, 2004·The Journal of Clinical Investigation·Cecile M FremondBernhard Ryffel
Mar 18, 2005·Annual Review of Immunology·Rebecca J GreenwaldArlene H Sharpe
Apr 6, 2005·International Journal of STD & AIDS·Helen McShane
Aug 30, 2005·International Journal for Parasitology·Luis I TerrazasMiriam Rodríguez-Sosa
Feb 28, 2006·Trends in Immunology·Taku Okazaki, Tasuku Honjo
Feb 17, 2007·Nature Immunology·Arlene H SharpeGordon J Freeman
Feb 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Eszter Lázár-MolnárJoshua D Nosanchuk
May 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jared H RoweSing Sing Way
Jun 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Javier O JuradoVerónica E García
Sep 3, 2008·Microbes and Infection·Daniel S KorbelUlrich E Schaible
Apr 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Xin HuangAlfred Ayala

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Citations

Oct 29, 2013·Nature Neuroscience·Allison R Bialas, Beth Stevens
Apr 9, 2011·Nature Reviews. Immunology·Gerhard WalzlAlimuddin Zumla
Aug 26, 2010·Nature Reviews. Microbiology·Sheilagh Molloy
Sep 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yuxiang RuiShunsuke Chikuma
Dec 12, 2012·The Journal of Experimental Medicine·Helge FrebelAnnette Oxenius
May 11, 2013·The Journal of Infectious Diseases·Suraj B Sable
Sep 27, 2012·Viruses·Gabrielle StackIan R Humphreys
Mar 5, 2014·Nature Reviews. Microbiology·Cláudio Nunes-AlvesSamuel M Behar
Jan 12, 2013·American Journal of Respiratory and Critical Care Medicine·Cheryl L DayWillem A Hanekom
Jul 30, 2014·American Journal of Respiratory and Critical Care Medicine·Nicole A BraunWonder P Drake
May 24, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Anhui YaoJian Wang
Oct 5, 2011·The Journal of Experimental Medicine·Bisweswar Nandi, Samuel M Behar
Mar 23, 2013·Annual Review of Immunology·Anne O'GarraMatthew P R Berry
Oct 1, 2011·Journal of Biomedicine & Biotechnology·Kimberly A HofmeyerXingxing Zang
Feb 13, 2016·International Journal of Clinical Oncology·Shunsuke Chikuma
Sep 10, 2015·The Journal of Infectious Diseases·Jacqueline M CliffHazel M Dockrell
Apr 4, 2013·Seminars in Immunology·Deanna A KulpaRafick-Pierre Sékaly
Jan 22, 2013·Trends in Immunology·Helge Frebel, Annette Oxenius
Mar 21, 2012·Tuberculosis·Marcela Henao-TamayoIan M Orme
Nov 19, 2011·Trends in Immunology·David M LoweAdrian R Martineau
Jan 11, 2011·Trends in Immunology·Egídio TorradoAndrea M Cooper
Jan 30, 2015·European Journal of Immunology·Jaclyn W McAleesIan P Lewkowich
Oct 30, 2013·European Journal of Immunology·Cortez McBerryJulio Aliberti
Feb 24, 2015·Immunological Reviews·JoAnne L FlynnPhilana Ling Lin
Sep 30, 2015·Immunity, Inflammation and Disease·Katrina M PollockAjit Lalvani
May 23, 2012·Current Opinion in Immunology·Andrea M Cooper, Egidio Torrado

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