Dectin-2 regulates the effector phase of house dust mite-elicited pulmonary inflammation independently from its role in sensitization

Matthew W. Parsons, Li Li, Aaron M. Wallace, Min Jung Lee, Howard R. Katz, James M. Fernandez, Shinobu Saijo, Yoichiro Iwakura, K. Frank Austen, Yoshihide Kanaoka, Nora A. Barrett

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Abstract

The myeloid C-type lectin receptor Dectin-2 directs the generation of Th2 and Th17 immune responses to the house dust mite Dermatophagoides farinae through the generation of cysteinyl leukotrienes and proinflammatory cytokines, respectively, but a role for Dectin-2 in effector phase responses has not been described. In this study, we demonstrate that administration of the Dectin-2 mAb solely at the time of D. farinae challenge abrogated eosinophilic and neutrophilic inflammation in the bronchoalveolar lavage fluid and Th1, Th2, and Th17 inflammation in the lung of previously sensitized mice. Furthermore, Dectin-2 null mice (Clec4n-/-) sensitized with the adoptive transfer of D. farinae-pulsed wild-type (WT) bone marrow-derived dendritic cells (DCs) also had less D. farinae-elicited pulmonary inflammation, supporting an effector function for Dectin-2. The protection from pulmonary inflammation seen with the Dectin-2 mAb or in Clec4n-/- mice was associated with little or no reduction in lung-draining lymph node cells or their cytokine production and with no reduction in serum IgE. WT and Clec4n-/- mice recipients, sensitized with D. farinae-pulsed WT bone marrow-derived DCs, had comparable levels of D. farinae-elicited IL-6, IL-23, TNF-α, and cysteinyl leukotrienes in the lung. By contrast, D. farinae-elicited CCL4 and CCL8 production from pulmonary CD11c+CD11b+Ly6C+ and CD11c+CD11b+Ly6C-CD64+ monocyte-derived DCs was reduced in Clec4n-/- recipients. Addition of CCL8 at the time of D. farinae challenge abrogated the protection from eosinophilic, neutrophilic, and Th2 pulmonary inflammation seen in Clec4n -/- recipients. Taken together, these results reveal that Dectin-2 regulates monocyte-derived DC function in the pulmonary microenvironment at D. farinae challenge to promote the local inflammatory response.

Original languageEnglish (US)
Pages (from-to)1361-1371
Number of pages11
JournalJournal of Immunology
Volume192
Issue number4
DOIs
StatePublished - Feb 15 2014

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Dermatophagoides farinae
Pyroglyphidae
Pneumonia
Dendritic Cells
Lung
Monocytes
Bone Marrow
Cytokines
C-Type Lectins
Interleukin-23
mouse dectin-2
Adoptive Transfer
Bronchoalveolar Lavage Fluid
Immunoglobulin E
Interleukin-6
Lymph Nodes
Inflammation

ASJC Scopus subject areas

  • Immunology

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Dectin-2 regulates the effector phase of house dust mite-elicited pulmonary inflammation independently from its role in sensitization. / Parsons, Matthew W.; Li, Li; Wallace, Aaron M.; Lee, Min Jung; Katz, Howard R.; Fernandez, James M.; Saijo, Shinobu; Iwakura, Yoichiro; Austen, K. Frank; Kanaoka, Yoshihide; Barrett, Nora A.

In: Journal of Immunology, Vol. 192, No. 4, 15.02.2014, p. 1361-1371.

Research output: Contribution to journalArticle

Parsons, MW, Li, L, Wallace, AM, Lee, MJ, Katz, HR, Fernandez, JM, Saijo, S, Iwakura, Y, Austen, KF, Kanaoka, Y & Barrett, NA 2014, 'Dectin-2 regulates the effector phase of house dust mite-elicited pulmonary inflammation independently from its role in sensitization', Journal of Immunology, vol. 192, no. 4, pp. 1361-1371. https://doi.org/10.4049/jimmunol.1301809
Parsons, Matthew W. ; Li, Li ; Wallace, Aaron M. ; Lee, Min Jung ; Katz, Howard R. ; Fernandez, James M. ; Saijo, Shinobu ; Iwakura, Yoichiro ; Austen, K. Frank ; Kanaoka, Yoshihide ; Barrett, Nora A. / Dectin-2 regulates the effector phase of house dust mite-elicited pulmonary inflammation independently from its role in sensitization. In: Journal of Immunology. 2014 ; Vol. 192, No. 4. pp. 1361-1371.
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abstract = "The myeloid C-type lectin receptor Dectin-2 directs the generation of Th2 and Th17 immune responses to the house dust mite Dermatophagoides farinae through the generation of cysteinyl leukotrienes and proinflammatory cytokines, respectively, but a role for Dectin-2 in effector phase responses has not been described. In this study, we demonstrate that administration of the Dectin-2 mAb solely at the time of D. farinae challenge abrogated eosinophilic and neutrophilic inflammation in the bronchoalveolar lavage fluid and Th1, Th2, and Th17 inflammation in the lung of previously sensitized mice. Furthermore, Dectin-2 null mice (Clec4n-/-) sensitized with the adoptive transfer of D. farinae-pulsed wild-type (WT) bone marrow-derived dendritic cells (DCs) also had less D. farinae-elicited pulmonary inflammation, supporting an effector function for Dectin-2. The protection from pulmonary inflammation seen with the Dectin-2 mAb or in Clec4n-/- mice was associated with little or no reduction in lung-draining lymph node cells or their cytokine production and with no reduction in serum IgE. WT and Clec4n-/- mice recipients, sensitized with D. farinae-pulsed WT bone marrow-derived DCs, had comparable levels of D. farinae-elicited IL-6, IL-23, TNF-α, and cysteinyl leukotrienes in the lung. By contrast, D. farinae-elicited CCL4 and CCL8 production from pulmonary CD11c+CD11b+Ly6C+ and CD11c+CD11b+Ly6C-CD64+ monocyte-derived DCs was reduced in Clec4n-/- recipients. Addition of CCL8 at the time of D. farinae challenge abrogated the protection from eosinophilic, neutrophilic, and Th2 pulmonary inflammation seen in Clec4n -/- recipients. Taken together, these results reveal that Dectin-2 regulates monocyte-derived DC function in the pulmonary microenvironment at D. farinae challenge to promote the local inflammatory response.",
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AU - Lee, Min Jung

AU - Katz, Howard R.

AU - Fernandez, James M.

AU - Saijo, Shinobu

AU - Iwakura, Yoichiro

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