Stress keratin 17 enhances papillomavirus infection-induced disease by downregulating T cell recruitment


Autoři: Wei Wang aff001;  Aayushi Uberoi aff002;  Megan Spurgeon aff001;  Ellery Gronski aff001;  Vladimir Majerciak aff003;  Alexei Lobanov aff004;  Mitchell Hayes aff001;  Amanda Loke aff001;  Zhi-Ming Zheng aff003;  Paul F. Lambert aff001
Působiště autorů: McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, United States of America aff001;  Department of Dermatology, University of Pennsylvania, Philadelphia, PA, United States of America aff002;  Tumor Virus RNA Biology Section, National Cancer Institute, Frederick, MD, United States of America aff003;  CCR Collaborative Bioinformatics Resource (CCBR), National Cancer Institute, Bethesda, MD, United States of America aff004
Vyšlo v časopise: Stress keratin 17 enhances papillomavirus infection-induced disease by downregulating T cell recruitment. PLoS Pathog 16(1): e1008206. doi:10.1371/journal.ppat.1008206
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008206

Souhrn

High-risk human papillomaviruses (HPVs) cause 5% of human cancers. Despite the availability of HPV vaccines, there remains a strong urgency to find ways to treat persistent HPV infections, as current HPV vaccines are not therapeutic for individuals already infected. We used a mouse papillomavirus infection model to characterize virus-host interactions. We found that mouse papillomavirus (MmuPV1) suppresses host immune responses via overexpression of stress keratins. In mice deficient for stress keratin K17 (K17KO), we observed rapid regression of papillomas dependent on T cells. Cellular genes involved in immune response were differentially expressed in the papillomas arising on the K17KO mice correlating with increased numbers of infiltrating CD8+ T cells and upregulation of IFNγ-related genes, including CXCL9 and CXCL10, prior to complete regression. Blocking the receptor for CXCL9/CXCL10 prevented early regression. Our data provide a novel mechanism by which papillomavirus-infected cells evade host immunity and defines new therapeutic targets for treating persistent papillomavirus infections.

Klíčová slova:

Cloning – Cytotoxic T cells – Ear infections – Flow cytometry – Immune response – Keratins – T cells – Papillomas


Zdroje

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