IL-4 receptor signaling is required for mannose receptor expression by macrophages recruited to granulomata but not resident cells in mice infected with Schistosoma mansoni

S A Linehan; P S Coulson; R A Wilson; A P Mountford; F Brombacher; L Martinez-Pomares; S Gordon

doi:10.1097/01.LAB.0000081392.93701.6F

IL-4 receptor signaling is required for mannose receptor expression by macrophages recruited to granulomata but not resident cells in mice infected with Schistosoma mansoni

S A Linehan, P S Coulson, R A Wilson, A P Mountford, F Brombacher, L Martinez-Pomares, S Gordon

Biology

Research output: Contribution to journal › Article › peer-review

Abstract

High levels of mannose receptor (MR) expression and pinocytic activity are a hallmark of Th2 cytokine-driven alternative MPhi activation in vitro. We examined expression of MR in situ and its regulation by Th1/Th2 cytokines in IL-4Ralpha -/- and wild-type (WT) mice challenged with Schistosoma mansoni. Parasite eggs induce a vigorous granulomatous response, driven by Th2 cytokines in WT mice, but by Th1 cytokines in IL-4Ra -/- mice. MR was expressed by granuloma MPhi in WT mice but not in IL-4Ralpha -/- mice, whose MPhi nevertheless exhibited a mature phenotype and morphology. By contrast expression of MR in resident tissue MPhi and endothelial cells appeared unaffected by Th1/Th2 cytokines. Our results revealed that Th1/Th2 cytokines differentially regulate MR according to cell type and play a critical role in regulating MR expression by MPhi recruited to granulomata. We also present evidence that components of schistosome eggs and a fraction of their secretions are ligands of MR, and suggest that MR activity may be of functional significance in the granulomatous response.

Original language	English
Pages (from-to)	1223-1231
Number of pages	9
Journal	Laboratory investigation
Volume	83
Issue number	8
DOIs	https://doi.org/10.1097/01.LAB.0000081392.93701.6F
Publication status	Published - Aug 2003

Keywords

MURINE MACROPHAGES
INTERFERON-GAMMA
IFN-GAMMA
IN-VITRO
ALTERNATIVE ACTIVATION
ENDOTHELIAL-CELLS
DENDRITIC CELLS
DOWN-REGULATION
DEFICIENT MICE
NITRIC-OXIDE

Access to Document

10.1097/01.LAB.0000081392.93701.6F

Cite this

Linehan, S. A., Coulson, P. S., Wilson, R. A., Mountford, A. P., Brombacher, F., Martinez-Pomares, L., & Gordon, S. (2003). IL-4 receptor signaling is required for mannose receptor expression by macrophages recruited to granulomata but not resident cells in mice infected with Schistosoma mansoni. Laboratory investigation, 83(8), 1223-1231. https://doi.org/10.1097/01.LAB.0000081392.93701.6F

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title = "IL-4 receptor signaling is required for mannose receptor expression by macrophages recruited to granulomata but not resident cells in mice infected with Schistosoma mansoni",

abstract = "High levels of mannose receptor (MR) expression and pinocytic activity are a hallmark of Th2 cytokine-driven alternative MPhi activation in vitro. We examined expression of MR in situ and its regulation by Th1/Th2 cytokines in IL-4Ralpha -/- and wild-type (WT) mice challenged with Schistosoma mansoni. Parasite eggs induce a vigorous granulomatous response, driven by Th2 cytokines in WT mice, but by Th1 cytokines in IL-4Ra -/- mice. MR was expressed by granuloma MPhi in WT mice but not in IL-4Ralpha -/- mice, whose MPhi nevertheless exhibited a mature phenotype and morphology. By contrast expression of MR in resident tissue MPhi and endothelial cells appeared unaffected by Th1/Th2 cytokines. Our results revealed that Th1/Th2 cytokines differentially regulate MR according to cell type and play a critical role in regulating MR expression by MPhi recruited to granulomata. We also present evidence that components of schistosome eggs and a fraction of their secretions are ligands of MR, and suggest that MR activity may be of functional significance in the granulomatous response.",

keywords = "MURINE MACROPHAGES, INTERFERON-GAMMA, IFN-GAMMA, IN-VITRO, ALTERNATIVE ACTIVATION, ENDOTHELIAL-CELLS, DENDRITIC CELLS, DOWN-REGULATION, DEFICIENT MICE, NITRIC-OXIDE",

author = "Linehan, {S A} and Coulson, {P S} and Wilson, {R A} and Mountford, {A P} and F Brombacher and L Martinez-Pomares and S Gordon",

year = "2003",

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Linehan, SA, Coulson, PS, Wilson, RA, Mountford, AP, Brombacher, F, Martinez-Pomares, L & Gordon, S 2003, 'IL-4 receptor signaling is required for mannose receptor expression by macrophages recruited to granulomata but not resident cells in mice infected with Schistosoma mansoni', Laboratory investigation, vol. 83, no. 8, pp. 1223-1231. https://doi.org/10.1097/01.LAB.0000081392.93701.6F

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T1 - IL-4 receptor signaling is required for mannose receptor expression by macrophages recruited to granulomata but not resident cells in mice infected with Schistosoma mansoni

AU - Linehan, S A

AU - Coulson, P S

AU - Wilson, R A

AU - Mountford, A P

AU - Brombacher, F

AU - Martinez-Pomares, L

AU - Gordon, S

PY - 2003/8

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N2 - High levels of mannose receptor (MR) expression and pinocytic activity are a hallmark of Th2 cytokine-driven alternative MPhi activation in vitro. We examined expression of MR in situ and its regulation by Th1/Th2 cytokines in IL-4Ralpha -/- and wild-type (WT) mice challenged with Schistosoma mansoni. Parasite eggs induce a vigorous granulomatous response, driven by Th2 cytokines in WT mice, but by Th1 cytokines in IL-4Ra -/- mice. MR was expressed by granuloma MPhi in WT mice but not in IL-4Ralpha -/- mice, whose MPhi nevertheless exhibited a mature phenotype and morphology. By contrast expression of MR in resident tissue MPhi and endothelial cells appeared unaffected by Th1/Th2 cytokines. Our results revealed that Th1/Th2 cytokines differentially regulate MR according to cell type and play a critical role in regulating MR expression by MPhi recruited to granulomata. We also present evidence that components of schistosome eggs and a fraction of their secretions are ligands of MR, and suggest that MR activity may be of functional significance in the granulomatous response.

AB - High levels of mannose receptor (MR) expression and pinocytic activity are a hallmark of Th2 cytokine-driven alternative MPhi activation in vitro. We examined expression of MR in situ and its regulation by Th1/Th2 cytokines in IL-4Ralpha -/- and wild-type (WT) mice challenged with Schistosoma mansoni. Parasite eggs induce a vigorous granulomatous response, driven by Th2 cytokines in WT mice, but by Th1 cytokines in IL-4Ra -/- mice. MR was expressed by granuloma MPhi in WT mice but not in IL-4Ralpha -/- mice, whose MPhi nevertheless exhibited a mature phenotype and morphology. By contrast expression of MR in resident tissue MPhi and endothelial cells appeared unaffected by Th1/Th2 cytokines. Our results revealed that Th1/Th2 cytokines differentially regulate MR according to cell type and play a critical role in regulating MR expression by MPhi recruited to granulomata. We also present evidence that components of schistosome eggs and a fraction of their secretions are ligands of MR, and suggest that MR activity may be of functional significance in the granulomatous response.

KW - MURINE MACROPHAGES

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KW - IFN-GAMMA

KW - IN-VITRO

KW - ALTERNATIVE ACTIVATION

KW - ENDOTHELIAL-CELLS

KW - DENDRITIC CELLS

KW - DOWN-REGULATION

KW - DEFICIENT MICE

KW - NITRIC-OXIDE

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DO - 10.1097/01.LAB.0000081392.93701.6F

M3 - Article

VL - 83

SP - 1223

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JO - Laboratory investigation

JF - Laboratory investigation

SN - 0023-6837

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