Toll-like Receptors Induce a Phagocytic Gene Program through p38

Sean E. Doyle, Ryan M. O'Connell, Gustavo A. Miranda, Sagar A. Vaidya, Edward K. Chow, Philip T. Liu, Shinobu Suzuki, Nobutaka Suzuki, Robert L. Modlin, Wen Chen Yeh, Timothy F Lane, Genhong Cheng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

314 Scopus citations


Toll-like receptor (TLR) signaling and phagocytosis are hallmarks of macrophage-mediated innate immune responses to bacterial infection. However, the relationship between these two processes is not well established. Our data indicate that TLK ligands specifically promote bacterial phagocytosis, in both murine and human cells, through induction of a phagocytic gene program. Importantly, TLR-induced phagocytosis of bacteria was found to be reliant on myeloid differentiation factor 88-dependent signaling through interleukin-1 receptor-associated kinase-4 and p38 leading to the up-regulation of scavenger receptors. Interestingly, individual TLRs promote phagocytosis to varying degrees with TLR9 being the strongest and TLR3 being the weakest inducer of this process. We also demonstrate that TLR ligands not only amplify the percentage of phagocytes uptaking Escherichia coli, but also increase the number of bacteria phagocytosed by individual macrophages. Taken together, our data describe an evolutionarily conserved mechanism by which TLRs can specifically promote phagocytic clearance of bacteria during infection.

Original languageEnglish (US)
Pages (from-to)81-90
Number of pages10
JournalJournal of Experimental Medicine
Issue number1
StatePublished - Jan 5 2004


  • Macrophage
  • P38
  • Phagocytosis
  • Scavenger receptor
  • Toll-like receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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