IFN-γ-mediated survival enables human neutrophils to produce MCP-1/CCL2 in response to activation by TLR ligands

Teizo Yoshimura, Munehisa Takahashi

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

TLRs are key elements of the pathogen recognition mechanism used by the host immune system. Neutrophils express almost all TLRs, and activation of TLRs, such as TLR2 and TLR4, has been shown to induce the production of proinflammatory cytokines and chemokines, potentially linking innate and adaptive immunity. In the present study, we investigated whether activation of TLRs induces neutrophil production of MCP-1/CCL2, a key mediator involved in the development of adaptive immunity. Activation of neutrophils with LPS, lipoteichoic acid, or N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]- Cys-[S]-Ser-[S]-Lys did not induce significant MCP-1 production and release; however, the Th1 cytokine IFN-γ dramatically up-regulated MCP-1 production in cells activated with each TLR ligand. The majority of MCP-1 was released between 24 and 48 h of culture, indicating that this is a late event. The effect of IFN-γ appeared to be due to its antiapoptotic effect, but not priming effect, revealing a biological consequence of IFN-γ-induced neutrophil survival. Although IFN-γ failed to protect neutrophils from cell death at a higher dose of LPS, the p38 MAPK inhibitor SB203580 dramatically increased MCP-1 release and neutrophil survival at this LPS concentration. Thus, p38 MAPK plays a previously uncharacterized role in neutrophil function. Taken together, our results indicate that human neutrophils produce MCP-1 in a Th1 microenvironment and this neutrophil-derived MCP-1 potentially amplifies the development of Th1 adaptive responses.

Original languageEnglish
Pages (from-to)1942-1949
Number of pages8
JournalJournal of Immunology
Volume179
Issue number3
Publication statusPublished - Aug 1 2007
Externally publishedYes

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Neutrophils
Ligands
Survival
Adaptive Immunity
p38 Mitogen-Activated Protein Kinases
Cytokines
Neutrophil Activation
Chemokines
Innate Immunity
Immune System
Cell Death

ASJC Scopus subject areas

  • Immunology

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IFN-γ-mediated survival enables human neutrophils to produce MCP-1/CCL2 in response to activation by TLR ligands. / Yoshimura, Teizo; Takahashi, Munehisa.

In: Journal of Immunology, Vol. 179, No. 3, 01.08.2007, p. 1942-1949.

Research output: Contribution to journalArticle

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