Role of Prostaglandins in age related defects in the Immune response against respiratory viral infections

One of the focuses of the Perlman lab is to study immunopathology caused by a respiratory virus, Severe Acute Respiratory Syndrome- Corona virus (SARS-CoV). Increasing defects in the immune system with age have been documented and shown to correlate with worse outcomes after various viral infections such as influenza A, West Nile and severe acute respiratory syndrome (SARS). In the 2002-2003 SARS epidemic more than half of the aged patients (> 65 years) died, while no mortality was observed in patients under 24 years of age.

I am interested in studying the role of prostaglandins in mediating/regulating age related defects in the immune response against respiratory viral infections especially SARS-CoV. Our lab recently reported the age related defects in migration of respiratory DCs to the draining LN, which further resulted in a weak T cell response following respiratory viral infections. This was found to be due to increased levels of PGD2 in the broncheo alveolar lavage fluid in aged mice. Blocking the effect of PGD2 by using a PGD2 receptor antagonist partially reversed these defects. My goal is to examine the source of PGD2 in the lungs of aged mice and also their potential targets.

Hua X, Vijay R, Channappanavar R, Athmer J, Meyerholz DK, Pagedar N, Tilley S, Perlman S. Nasal priming by a murine coronavirus provides protective immunity against lethal heterologous virus pneumonia. JCI Insight. 2018 Jun 7;3(11). pii: 99025. doi: 10.1172/jci.insight.99025. [Epub ahead of print] PubMed PMID:29875310; PubMed Central PMCID: PMC6124400.

Vijay R, Fehr AR, Janowski AM, Athmer J, Wheeler DL, Grunewald M, Sompallae R Kurup SP, Meyerholz DK, Sutterwala FS, Narumiya S, Perlman S. Virus-induced inflammasome activation is suppressed by prostaglandin D(2)/DP1 signaling. Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5444-E5453. doi:10.1073/pnas.1704099114. Epub 2017 Jun 19. PubMed PMID: 28630327; PubMed Central PMCID: PMC5502630.

Zhao J, Vijay R, Zhao J, Gale M Jr, Diamond MS, Perlman S. MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis. J Virol. 2016 Jul 27;90(16):7098-7108. doi: 10.1128/JVI.00707-16. Print 2016 Aug 15. PubMed PMID: 27226371; PubMed Central PMCID: PMC4984631.

Perlman S, Vijay R. Middle East respiratory syndrome vaccines. Int J Infect Dis. 2016 Jun;47:23-8. doi: 10.1016/j.ijid.2016.04.008. Epub 2016 Apr 7. Review. PubMed PMID: 27062985; PubMed Central PMCID: PMC4969153.

Channappanavar R, Fehr AR, Vijay R, Mack M, Zhao J, Meyerholz DK, Perlman S. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe. 2016 Feb 10;19(2):181-93. doi: 10.1016/j.chom.2016.01.007. PubMed PMID: 26867177; PubMed Central PMCID: PMC4752723.

Vijay R, Perlman S. Middle East respiratory syndrome and severe acute respiratory syndrome. Curr Opin Virol. 2016 Feb;16:70-76. doi: 10.1016/j.coviro.2016.01.011. Epub 2016 Feb 12. Review. PubMed PMID: 26855039; PubMed Central PMCID: PMC4821769.

Vijay R, Hua X, Meyerholz DK, Miki Y, Yamamoto K, Gelb M, Murakami M, Perlman S. Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection. J Exp Med. 2015 Oct 19;212(11):1851-68. doi: 10.1084/jem.20150632. Epub 2015 Sep 21. PubMed PMID:26392224; PubMed Central PMCID: PMC4612096.