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Eradication of the commensal intestinal microflora by oral antimicrobials interferes with the host response to lipopolysaccharide

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Abstract

The host components and commensal microorganisms of the intestinal microenvironment play roles in the development and maintenance of the host defence. Recent observations have suggested that toll-like receptors (TLRs) are involved in the recognition of innate immunity against intestinal microbes. However, little is known regarding the role of TLR in the maintenance of systemic host defence by intestinal microorganisms. We studied the expression and function of TLR4 and TLR2 on alveolar and peritoneal macrophages in mice after 3 weeks of oral administration of streptomycin and cefotaxime. After active treatment, the intestinal microorganisms were nearly completely eradicated, and the surface expression of TLR4 and TLR2 on the peritoneal macrophages was prominently downregulated. When the actively treated mice were challenged with lipopolysaccharide (LPS), a TLR4 ligand, the host response was markedly impaired. Our results suggest that the oral administration of antimicrobials downregulates the expression of surface TLR on the peritoneal macrophages and modulates the host immune responses against LPS by modifying the intestinal environment.

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Acknowledgement

This study was partially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (#18591988 for NS) and was not commercially supported. The authors thank Rodolphe Ruffy, MD, for reviewing the style and language of this manuscript.

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Authors and Affiliations

  1. Department of Anesthesiology and Intensive Care, University Hospital, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyoku, Kyoto, 602-8566, Japan

    T. Umenai, N. Shime & Y. Tanaka

  2. Department of Microbiology and Immunology, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan

    H. Hirai, M. Kita & J. Imanishi

  3. International Research Centre for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan

    T. Nakaya

  4. Yakult Central Institute for Microbiological Research, Tokyo, 186-8650, Japan

    T. Asahara & K. Nomoto

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  1. T. Umenai
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Correspondence to N. Shime.

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Umenai, T., Hirai, H., Shime, N. et al. Eradication of the commensal intestinal microflora by oral antimicrobials interferes with the host response to lipopolysaccharide. Eur J Clin Microbiol Infect Dis 29, 633–641 (2010). https://doi.org/10.1007/s10096-010-0905-3

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  • DOI: https://doi.org/10.1007/s10096-010-0905-3

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