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Salmonella Fimbrial Protein FimH Is Involved in Expression of Proinflammatory Cytokines in a Toll-Like Receptor

Kei-Ichi Uchiya1, Yurie Kamimura2, Ayumi Jusakon2

  • 1Department of Microbiology, Faculty of Pharmacy, Meijo University, Nagoya, Japan kuchiya@meijo-u.ac.jp.

Infection and Immunity
|January 4, 2019
PubMed

Insights

The FimH protein on Salmonella Typhimurium triggers proinflammatory cytokine release in macrophages by activating Toll-like receptor 4 (TLR4). This interaction is crucial for the immune response to bacterial infection.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • Type 1 fimbriae are bacterial surface structures crucial for adhesion.
  • FimH, the tip adhesin of type 1 fimbriae, plays a role in bacterial interactions with host cells.
  • Salmonella Typhimurium infection elicits an inflammatory response in macrophages.

Purpose of the Study:

  • To investigate the role of type 1 fimbriae, specifically FimH, in the expression of proinflammatory cytokines during Salmonella Typhimurium infection.
  • To elucidate the molecular mechanisms by which FimH influences cytokine production in macrophages.

Main Methods:

  • Infection of macrophages with wild-type and mutant Salmonella Typhimurium strains (fimA, fimH).
  • Treatment of macrophages with purified recombinant FimH and FimA proteins.
  • Analysis of cytokine mRNA levels (IL-1β, IL-6, TNF-α) and activation of signaling pathways (MAPK, NF-κB).
  • Inhibition studies using TLR4 inhibitor TAK-242 and polymyxin B.
  • Stimulation of HEK293 cells expressing TLR4 and co-receptors (MD-2/CD14).

Main Results:

  • Macrophages infected with fimA or fimH mutants showed lower IL-1β mRNA levels compared to wild-type infection.
  • Recombinant FimH, but not FimA, activated MAPK and NF-κB pathways, inducing IL-1β, IL-6, and TNF-α expression.
  • FimH-induced cytokine expression was dependent on TLR4 and required MD-2/CD14 co-receptors.
  • Specific FimH variants (N-terminal deletion, heat-treated) failed to induce these effects.

Conclusions:

  • FimH acts as a pathogen-associated molecular pattern (PAMP) in Salmonella Typhimurium.
  • FimH is recognized by the TLR4 receptor complex (TLR4/MD-2/CD14) on host cells.
  • FimH plays a significant role in inducing proinflammatory cytokine expression in Salmonella-infected macrophages, contributing to the host immune response.
Keywords:
FimHSalmonella enterica serovar TyphimuriumToll-like receptor 4proinflammatory cytokinestype 1 fimbriae

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