Distinct Signaling Pathways Between Human Macrophages and Primary Gingival Epithelial Cells by Aggregatibacter actinomycetemcomitans

Autor(es)

Ando-Suguimoto, Ellen S. ^[1] ; Benakanakere, Manjunatha R. ^[2] ; Mayer, Marcia P. A. ^[1] ; Kinane, Denis F. ^[3]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, BR-05508020 Sao Paulo - Brazil

^[2] Univ Penn, Sch Dent Med, Dept Periodont, Philadelphia, PA 19104 - USA

^[3] Univ Geneva, Sch Dent Med, Dept Periodontol, Fac Med, CH-12114 Geneva - Switzerland

• Tipo de documento: Artigo Científico
• Fonte: PATHOGENS; v. 9, n. 4 APR 2020.
• Citações Web of Science: 0

Resumo

In aggressive periodontitis, the dysbiotic microbial community in the subgingival crevice, which is abundant in Aggregatibacter actinomycetemcomitans, interacts with extra- and intracellular receptors of host cells, leading to exacerbated inflammation and subsequent tissue destruction. Our goal was to understand the innate immune interactions of A. actinomycetemcomitans with macrophages and human gingival epithelial cells (HGECs) on the signaling cascade involved in inflammasome and inflammatory responses. U937 macrophages and HGECs were co-cultured with A. actinomycetemcomitans strain Y4 and key signaling pathways were analyzed using real-time PCR, Western blotting and cytokine production by ELISA. A. actinomycetemcomitans infection upregulated the transcription of TLR2, TLR4, NOD2 and NLRP3 in U937 macrophages, but not in HGECs. Transcription of IL-1 beta and IL-18 was upregulated in macrophages and HGECs after 1 h interaction with A. actinomycetemcomitans, but positive regulation persisted only in macrophages, resulting in the presence of IL-1 beta in macrophage supernatant. Immunoblot data revealed that A. actinomycetemcomitans induced the phosphorylation of AKT and ERK1/2, possibly leading to activation of the NF-kappa B pathway in macrophages. On the other hand, HGEC signaling induced by A. actinomycetemcomitans was distinct, since AKT and 4EBP1 were phosphorylated after stimulation with A. actinomycetemcomitans, whereas ERK1/2 was not. Furthermore, A. actinomycetemcomitans was able to induce the cleavage of caspase-1 in U937 macrophages in an NRLP3-dependent pathway. Differences in host cell responses, such as those seen between HGECs and macrophages, suggested that survival of A. actinomycetemcomitans in periodontal tissues may be favored by its ability to differentially activate host cells. (AU)

• Processo FAPESP: 12/05887-0 - Análise do efeito da toxina distensora citoletal (CDT) na ativação de inflamassomas
• Beneficiário: Ellen Sayuri Ando Suguimoto
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 15/18273-9 - Novas estratégias para o controle das periodontites
• Beneficiário: Marcia Pinto Alves Mayer
• Modalidade de apoio: Auxílio à Pesquisa - Temático