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High‐throughput sequencing reveals key genes and immune homeostatic pathways activated in myeloid dendritic cells by Porphyromonas gingivalis 381 and its fimbrial mutants
Author(s) -
Arjunan P.,
ElAwady A.,
Dannebaum R.O.,
KundeRamamoorthy G.,
Cutler C.W.
Publication year - 2016
Publication title -
molecular oral microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 77
eISSN - 2041-1014
pISSN - 2041-1006
DOI - 10.1111/omi.12131
Subject(s) - porphyromonas gingivalis , biology , fimbria , immune system , transcriptome , microbiology and biotechnology , dysbiosis , immunology , gene , gut flora , gene expression , genetics , escherichia coli , bacteria
Summary The human microbiome consists of highly diverse microbial communities that colonize our skin and mucosal surfaces, aiding in maintenance of immune homeostasis. The keystone pathogen Porphyromonas gingivalis induces a dysbiosis and disrupts immune homeostasis through as yet unclear mechanisms. The fimbrial adhesins of P. gingivalis facilitate biofilm formation, invasion of and dissemination by blood dendritic cells; hence, fimbriae may be key factors in disruption of immune homeostasis. In this study we employed RNA ‐seqencing transcriptome profiling to identify differentially expressed genes ( DEG s) in human monocyte‐derived dendritic cells (Mo DC s) in response to in vitro infection/exposure by Pg 381 or its isogenic mutant strains that solely express minor‐Mfa1 fimbriae ( DPG 3), major‐FimA fimbriae ( MFI ) or are deficient in both fimbriae ( MFB ) relative to uninfected control. Our results yielded a total of 479 DEG s that were at least two‐fold upregulated and downregulated in Mo DC s significantly ( P ≤ 0.05) by all four strains and certain DEG s that were strain‐specific. Interestingly, the gene ontology biological and functional analysis shows that the upregulated genes in DPG 3‐induced Mo DC s were more significant than other strains and associated with inflammation, immune response, anti‐apoptosis, cell proliferation, and other homeostatic functions. Both transcriptome and quantitative polymerase chain reaction results show that DPG 3, which solely expresses Mfa1, increased ZNF 366, CD 209, LOX 1, IDO 1, IL ‐10, CCL 2, SOCS 3, STAT 3 and FOXO 1 gene expression. In conclusion, we have identified key DC ‐mediated immune homeostatic pathways that could contribute to dysbiosis in periodontal infection with P. gingivalis .