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 language | English |
|---|---|
| Pages (from-to) | 1942-1949 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 179 |
| Issue number | 3 |
| Publication status | Published - Aug 1 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - IFN-γ-mediated survival enables human neutrophils to produce MCP-1/CCL2 in response to activation by TLR ligands
AU - Yoshimura, Teizo
AU - Takahashi, Munehisa
PY - 2007/8/1
Y1 - 2007/8/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 17641061
AN - SCOPUS:34548609509
VL - 179
SP - 1942
EP - 1949
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 3
ER -