Reese Tiffany A, Bi Kevin, Kambal Amal, Filali-Mouhim Ali, Beura Lalit K, Bürger Matheus C, Pulendran Bali, Sekaly Rafick-Pierre, Jameson Stephen C, Masopust David, Haining W Nicholas, Virgin Herbert W
Departments of Immunology and Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Pediatric Hematology and Oncology, Children's Hospital, Boston, MA 02115, and the Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Cell Host Microbe. 2016 May 11;19(5):713-9. doi: 10.1016/j.chom.2016.04.003. Epub 2016 Apr 20.
Immune responses differ between laboratory mice and humans. Chronic infection with viruses and parasites are common in humans, but are absent in laboratory mice, and thus represent potential contributors to inter-species differences in immunity. To test this, we sequentially infected laboratory mice with herpesviruses, influenza, and an intestinal helminth and compared their blood immune signatures to mock-infected mice before and after vaccination against yellow fever virus (YFV-17D). Sequential infection altered pre- and post-vaccination gene expression, cytokines, and antibodies in blood. Sequential pathogen exposure induced gene signatures that recapitulated those seen in blood from pet store-raised versus laboratory mice, and adult versus cord blood in humans. Therefore, basal and vaccine-induced murine immune responses are altered by infection with agents common outside of barrier facilities. This raises the possibility that we can improve mouse models of vaccination and immunity by selective microbial exposure of laboratory animals to mimic that of humans.
实验小鼠和人类的免疫反应存在差异。病毒和寄生虫的慢性感染在人类中很常见，但在实验小鼠中不存在，因此可能是种间免疫差异的潜在因素。为了验证这一点，我们先后用疱疹病毒、流感病毒和一种肠道蠕虫感染实验小鼠，并将它们在接种黄热病病毒（YFV-17D）疫苗前后的血液免疫特征与模拟感染的小鼠进行比较。连续感染改变了接种疫苗前后血液中的基因表达、细胞因子和抗体。连续接触病原体诱导的基因特征与宠物店饲养的小鼠和实验小鼠、人类成人和脐带血中的血液特征相似。因此，屏障设施外常见病原体的感染会改变基础和疫苗诱导的小鼠免疫反应。这增加了一种可能性，即我们可以通过选择性地让实验动物接触微生物来模拟人类的情况，从而改进疫苗接种和免疫的小鼠模型。
