Modulation of Alveolar Macrophages by Postimmunobiotics: Impact on TLR3-Mediated Antiviral Respiratory Immunity

Cells. 2022 Sep 25;11(19):2986. doi: 10.3390/cells11192986.

Abstract

Beneficial microbes with immunomodulatory capacities (immunobiotics) and their non-viable forms (postimmunobiotics) could be effectively utilized in formulations towards the prevention of respiratory viral infections. In this study, novel immunobiotic strains with the ability to increase antiviral immunity in porcine alveolar macrophages were selected from a library of Lactobacillus gasseri. Postimmunobiotics derived from the most remarkable strains were also evaluated in their capacity to modulate the immune response triggered by Toll-like receptor 3 (TLR3) in alveolar macrophages and to differentially regulate TLR3-mediated antiviral respiratory immunity in infant mice. We provide evidence that porcine alveolar macrophages (3D4/31 cells) are a useful in vitro tool for the screening of new antiviral immunobiotics and postimmunobiotics by assessing their ability to modulate the expression IFN-β, IFN-λ1, RNAseL, Mx2, and IL-6, which can be used as prospective biomarkers. We also demonstrate that the postimmunobiotics derived from the Lactobacillus gasseri TMT36, TMT39 and TMT40 (HK36, HK39 or HK40) strains modulate the innate antiviral immune response of alveolar macrophages and reduce lung inflammatory damage triggered by TLR3 activation in vivo. Although our findings should be deepened and expanded, the results of the present work provide a scientific rationale for the use of nasally administered HK36, HK39 or HK40 to beneficially modulate TLR3-triggerd respiratory innate immune response.

Keywords: Lactobacillus gasseri; TLR3; immunobiotics; lung inflammatory damage; porcine alveolar macrophages; postimmunobiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents
  • Immunity, Innate
  • Interleukin-6
  • Macrophages, Alveolar*
  • Mice
  • Swine
  • Toll-Like Receptor 3*

Substances

  • Antiviral Agents
  • Interleukin-6
  • TLR3 protein, mouse
  • Toll-Like Receptor 3

Grants and funding

This study was supported by ANPCyT-FONCyT grants PICT-2016-0410 and PICT-2018-03264 to Julio Villena. This study was also supported by Grant-in-Aid for Scientific Research (A) (19H00965) and Grant-in-Aid for JSPS fellows (21F50394) from the Japan Society for the Promotion of Science (JSPS), and by the research program on development of innovative technology grants (JPJ007097) from the Project of the Bio-oriented Technology Research Advancement Institution (BRAIN) to Haruki Kitazawa, and by JSPS Core-to-Core Program, A. Advanced Research Networks entitled Establishment of international agricultural immunology research-core for a quantum improvement in food safety. Mikado Tomokiyo and Kohtaro Fukuyama were supported by Japan Science and Technology Agency, SPRING, Grant Number JPMJSP2114 and the establishment of university fellowships towards the creation of science technology innovation, Grant Number JPMJFS2102, respectively.