Zeng Melody Y, Cisalpino Daniel, Varadarajan Saranyaraajan, Hellman Judith, Warren H Shaw, Cascalho Marilia, Inohara Naohiro, Núñez Gabriel
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
Immunity. 2016 Mar 15;44(3):647-658. doi: 10.1016/j.immuni.2016.02.006. Epub 2016 Mar 2.
The gut microbiota is compartmentalized in the intestinal lumen and induces local immune responses, but it remains unknown whether the gut microbiota can induce systemic response and contribute to systemic immunity. We report that selective gut symbiotic gram-negative bacteria were able to disseminate systemically to induce immunoglobulin G (IgG) response, which primarily targeted gram-negative bacterial antigens and conferred protection against systemic infections by E. coli and Salmonella by directly coating bacteria to promote killing by phagocytes. T cells and Toll-like receptor 4 on B cells were important in the generation of microbiota-specific IgG. We identified murein lipoprotein (MLP), a highly conserved gram-negative outer membrane protein, as a major antigen that induced systemic IgG homeostatically in both mice and humans. Administration of anti-MLP IgG conferred crucial protection against systemic Salmonella infection. Thus, our findings reveal an important function for the gut microbiota in combating systemic infection through the induction of protective IgG.
肠道微生物群在肠腔内呈区室化分布，并诱导局部免疫反应，但肠道微生物群是否能诱导全身反应并促进全身免疫仍不清楚。我们报告称，选择性肠道共生革兰氏阴性菌能够全身扩散以诱导免疫球蛋白G（IgG）反应，该反应主要针对革兰氏阴性菌抗原，并通过直接包裹细菌以促进吞噬细胞杀伤，从而对大肠杆菌和沙门氏菌的全身感染提供保护。T细胞和B细胞上的Toll样受体4在微生物群特异性IgG的产生中起重要作用。我们鉴定出胞壁酰脂蛋白（MLP），一种高度保守的革兰氏阴性菌外膜蛋白，是在小鼠和人类中均能稳态诱导全身IgG的主要抗原。给予抗MLP IgG可对全身沙门氏菌感染提供关键保护。因此，我们的研究结果揭示了肠道微生物群通过诱导保护性IgG在对抗全身感染中的重要作用。
