1. TLR2/TLR4 activation induces Tregs and suppresses intestinal inflammation caused by Fusobacterium nucleatum in vivo
- Author
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Bin Tang, Qian Li, Yang Xiang, Xuhu Mao, Zhu-jun Zhang, Yin-ping Jia, Chun-yu Hu, Ya-nan Tong, Dan Han, and Kun Wang
- Subjects
0301 basic medicine ,Male ,Physiology ,medicine.medical_treatment ,Cell Lines ,lcsh:Medicine ,Pathology and Laboratory Medicine ,Immune Receptors ,Biochemistry ,T-Lymphocytes, Regulatory ,Mice ,0302 clinical medicine ,Cell Signaling ,Immune Physiology ,Cellular types ,Medicine and Health Sciences ,Membrane Receptor Signaling ,Receptor ,lcsh:Science ,Toll-like Receptors ,Immune Response ,Mice, Knockout ,Innate Immune System ,Multidisciplinary ,Immune System Proteins ,biology ,Immune cells ,FOXP3 ,Regulatory T cells ,Middle Aged ,Immune Receptor Signaling ,Intestines ,Cytokine ,030220 oncology & carcinogenesis ,White blood cells ,Cytokines ,Female ,Biological Cultures ,medicine.symptom ,Research Article ,Signal Transduction ,Adult ,Blood cells ,Immunology ,T cells ,Inflammation ,Gastroenterology and Hepatology ,Research and Analysis Methods ,Proinflammatory cytokine ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,medicine ,Animals ,Humans ,Fusobacterium nucleatum ,Inflammatory Bowel Disease ,lcsh:R ,Biology and Life Sciences ,Proteins ,Cell Biology ,Molecular Development ,biology.organism_classification ,Microarray Analysis ,Toll-Like Receptor 2 ,Toll-Like Receptor 4 ,TLR2 ,stomatognathic diseases ,030104 developmental biology ,Animal cells ,Immune System ,TLR4 ,Fusobacterium Infections ,lcsh:Q ,Caco-2 Cells ,Developmental Biology - Abstract
Toll-like receptors (TLRs) 2 and 4 play critical roles in intestinal inflammation caused by Fusobacterium nucleatum (F. nucleatum) infection, but the role of TLR2/TLR4 in regulation of proinflammatory cytokines remains unknown. In this study, through microarray analysis and qRT-PCR, we showed that TLR2/TLR4 are involved in the F. nucleatum-induced inflammatory signaling pathway in Caco-2 cells, C57BL/6 mice and human clinical specimens. In TLR2-/- and TLR4-/- mice, F. nucleatum infection resulted in increased colonization of the bacteria and production of the proinflammatory cytokines IL-8, IL-1β and TNF-α. In addition, the ratio of Foxp3+ CD4+ T cells in the total CD4+ T cells in TLR2-/- and TLR4-/- mice was less than that in wild-type mice, and the ratio in hybrid mice was more than that in knockout mice, which suggested that TLR2/TLR4 mediated the number of Tregs. Furthermore, it was observed that inflammatory cytokine levels were reduced in TLR2-/- mice after Treg transfer. Thus, these data indicate that TLR2/TLR4 regulate F. nucleatum-induced inflammatory cytokines through Tregs in vivo.
- Published
- 2017