title: Imprinted DC mediate the immune-educating effect of early-life microbial exposure.
abstract: It has been long proposed that exposure to environmental factors early in life may have an educating effect on the development of immune regulatory functions. However, experimental studies on this issue are limited and the related molecular and cellular basis remains unclear. Here we report that neonatal exposure to killed bacteria (Chlamydia muridarum, originally called Chlamydia trachomatis mouse pneumonitis (MoPn)) changed the pattern of the hosts' immune responses to a model allergen (OVA) in adulthood. This was associated with altered phenotype and function of DC. We found that DC from adult mice treated neonatally with UV-killed MoPn exhibited distinct patterns of surface marker and TLR expression and cytokine production from control mice (DC from adult mice neonatally treated with vehicle, (Sham-DC)). More importantly, DC from adult mice treated neonatally with UV-killed MoPn induced significantly lower type-2 antigen-specific T-cell responses than Sham-DC shown in DC:T co-culture experiments in vitro and in adoptive transfer experiments in vivo. In addition, depletion of T cells in vivo largely abolished the phenotypic and functional alterations of DC caused by bacterial exposure, suggesting the involvement of T cell in this process. Our study demonstrates a central role of DC in linking the early-life exposure to microbial products and the balanced development of immune regulatory functions and the involvement of T cells in imprinting of the DC function.
authors.affiliation: Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Man, Canada.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiao
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Han
authors.forename: Shuhe
authors.initials: S
authors.lastname: Wang
authors.forename: Yijun
authors.initials: Y
authors.lastname: Fan
authors.forename: Megan
authors.initials: M
authors.lastname: Yang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Qiu
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D002454:Cell Differentiation / Q000276:immunology; D002690:Chlamydia Infections / Q000276:immunology; D023502:Chlamydia muridarum / Q000276:immunology*; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology*; D005260:Female; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
chemical_list: D016207:Cytokines; D010047:Ovalbumin