Toll-like Receptors Induce a Phagocytic Gene Program through p38

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

Research output: Contribution to journalArticle

297 Citations (Scopus)

Abstract

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
Volume199
Issue number1
DOIs
StatePublished - Jan 5 2004

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Toll-Like Receptors
Phagocytosis
Genes
Bacteria
Interleukin-1 Receptor-Associated Kinases
Myeloid Differentiation Factor 88
Macrophages
Ligands
Scavenger Receptors
Phagocytes
Bacterial Infections
Innate Immunity
Up-Regulation
Escherichia coli
Infection

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Doyle, S. E., O'Connell, R. M., Miranda-Carboni, G., Vaidya, S. A., Chow, E. K., Liu, P. T., ... Cheng, G. (2004). Toll-like Receptors Induce a Phagocytic Gene Program through p38. Journal of Experimental Medicine, 199(1), 81-90. https://doi.org/10.1084/jem.20031237

Toll-like Receptors Induce a Phagocytic Gene Program through p38. / Doyle, Sean E.; O'Connell, Ryan M.; Miranda-Carboni, Gustavo; Vaidya, Sagar A.; Chow, Edward K.; Liu, Philip T.; Suzuki, Shinobu; Suzuki, Nobutaka; Modlin, Robert L.; Yeh, Wen Chen; Lane, Timothy F.; Cheng, Genhong.

In: Journal of Experimental Medicine, Vol. 199, No. 1, 05.01.2004, p. 81-90.

Research output: Contribution to journalArticle

Doyle, SE, O'Connell, RM, Miranda-Carboni, G, Vaidya, SA, Chow, EK, Liu, PT, Suzuki, S, Suzuki, N, Modlin, RL, Yeh, WC, Lane, TF & Cheng, G 2004, 'Toll-like Receptors Induce a Phagocytic Gene Program through p38', Journal of Experimental Medicine, vol. 199, no. 1, pp. 81-90. https://doi.org/10.1084/jem.20031237
Doyle, Sean E. ; O'Connell, Ryan M. ; Miranda-Carboni, Gustavo ; Vaidya, Sagar A. ; Chow, Edward K. ; Liu, Philip T. ; Suzuki, Shinobu ; Suzuki, Nobutaka ; Modlin, Robert L. ; Yeh, Wen Chen ; Lane, Timothy F. ; Cheng, Genhong. / Toll-like Receptors Induce a Phagocytic Gene Program through p38. In: Journal of Experimental Medicine. 2004 ; Vol. 199, No. 1. pp. 81-90.
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