MyD88 is necessary for neutrophil recruitment in hypersensitivity pneumonitis

Stephanie C. Nance, Ae-Kyung Yi, Fabio C. Re, Elizabeth Fitzpatrick

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Hypersensitivity pneumonitis is an interstitial lung disease that is characterized by alveolitis, granuloma formation, and in some patients, fibrosis. Using the Saccharopolyspora rectivirgula animal model of Farmer's lung disease, our laboratory has demonstrated that neutrophils play a critical role in IFN-γ production during the acute phase of the disease. As IFN-γ is necessary for granuloma formation, it is important to identify the factors that lead to neutrophil recruitment during disease. To begin to identify the pattern recognition receptors (PRRs) that initiate chemokine production, leading to neutrophil recruitment following S. rectivirgula exposure, we examined the role of MyD88 and TLR2. Our results demonstrate that neutrophil recruitment, as measured by flow cytometry and the myeloperoxidase assay, was abolished in the absence of MyD88 following S. rectivirgula exposure. The decrease in neutrophil recruitment was likely a result of a significant decrease in production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine. These results suggest that S. rectivirgula interacts with PRRs that are upstream of the MyD88 pathway to initiate cytokine and chemokine production. In vitro studies suggest that S. rectivirgula can interact with TLR2, and stimulation of adherent cells from TLR2 knockout (KO) mice with S. rectivirgula resulted in a significant decrease in MIP-2 production. However, TLR2 KO mice did not have a reduction in neutrophil recruitment compared with wild-type mice following S. rectivirgula exposure. The results from our studies suggest that one or more PRR(s) upstream of MyD88 are necessary for neutrophil recruitment following S. rectivirgula exposure.

Original languageEnglish (US)
Pages (from-to)1207-1217
Number of pages11
JournalJournal of Leukocyte Biology
Volume83
Issue number5
DOIs
StatePublished - May 1 2008

Fingerprint

Extrinsic Allergic Alveolitis
Neutrophil Infiltration
Pattern Recognition Receptors
Granuloma
Chemokines
Knockout Mice
Neutrophils
Saccharopolyspora
Farmer's Lung
Chemokine CXCL2
Interstitial Lung Diseases
Acute Disease
Peroxidase
Lung Diseases
Flow Cytometry
Fibrosis
Animal Models
Cytokines

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

MyD88 is necessary for neutrophil recruitment in hypersensitivity pneumonitis. / Nance, Stephanie C.; Yi, Ae-Kyung; Re, Fabio C.; Fitzpatrick, Elizabeth.

In: Journal of Leukocyte Biology, Vol. 83, No. 5, 01.05.2008, p. 1207-1217.

Research output: Contribution to journalArticle

@article{61691edcd4224636851d6f92a3f7e133,
title = "MyD88 is necessary for neutrophil recruitment in hypersensitivity pneumonitis",
abstract = "Hypersensitivity pneumonitis is an interstitial lung disease that is characterized by alveolitis, granuloma formation, and in some patients, fibrosis. Using the Saccharopolyspora rectivirgula animal model of Farmer's lung disease, our laboratory has demonstrated that neutrophils play a critical role in IFN-γ production during the acute phase of the disease. As IFN-γ is necessary for granuloma formation, it is important to identify the factors that lead to neutrophil recruitment during disease. To begin to identify the pattern recognition receptors (PRRs) that initiate chemokine production, leading to neutrophil recruitment following S. rectivirgula exposure, we examined the role of MyD88 and TLR2. Our results demonstrate that neutrophil recruitment, as measured by flow cytometry and the myeloperoxidase assay, was abolished in the absence of MyD88 following S. rectivirgula exposure. The decrease in neutrophil recruitment was likely a result of a significant decrease in production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine. These results suggest that S. rectivirgula interacts with PRRs that are upstream of the MyD88 pathway to initiate cytokine and chemokine production. In vitro studies suggest that S. rectivirgula can interact with TLR2, and stimulation of adherent cells from TLR2 knockout (KO) mice with S. rectivirgula resulted in a significant decrease in MIP-2 production. However, TLR2 KO mice did not have a reduction in neutrophil recruitment compared with wild-type mice following S. rectivirgula exposure. The results from our studies suggest that one or more PRR(s) upstream of MyD88 are necessary for neutrophil recruitment following S. rectivirgula exposure.",
author = "Nance, {Stephanie C.} and Ae-Kyung Yi and Re, {Fabio C.} and Elizabeth Fitzpatrick",
year = "2008",
month = "5",
day = "1",
doi = "10.1189/jlb.0607391",
language = "English (US)",
volume = "83",
pages = "1207--1217",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "FASEB",
number = "5",

}

TY - JOUR

T1 - MyD88 is necessary for neutrophil recruitment in hypersensitivity pneumonitis

AU - Nance, Stephanie C.

AU - Yi, Ae-Kyung

AU - Re, Fabio C.

AU - Fitzpatrick, Elizabeth

PY - 2008/5/1

Y1 - 2008/5/1

N2 - Hypersensitivity pneumonitis is an interstitial lung disease that is characterized by alveolitis, granuloma formation, and in some patients, fibrosis. Using the Saccharopolyspora rectivirgula animal model of Farmer's lung disease, our laboratory has demonstrated that neutrophils play a critical role in IFN-γ production during the acute phase of the disease. As IFN-γ is necessary for granuloma formation, it is important to identify the factors that lead to neutrophil recruitment during disease. To begin to identify the pattern recognition receptors (PRRs) that initiate chemokine production, leading to neutrophil recruitment following S. rectivirgula exposure, we examined the role of MyD88 and TLR2. Our results demonstrate that neutrophil recruitment, as measured by flow cytometry and the myeloperoxidase assay, was abolished in the absence of MyD88 following S. rectivirgula exposure. The decrease in neutrophil recruitment was likely a result of a significant decrease in production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine. These results suggest that S. rectivirgula interacts with PRRs that are upstream of the MyD88 pathway to initiate cytokine and chemokine production. In vitro studies suggest that S. rectivirgula can interact with TLR2, and stimulation of adherent cells from TLR2 knockout (KO) mice with S. rectivirgula resulted in a significant decrease in MIP-2 production. However, TLR2 KO mice did not have a reduction in neutrophil recruitment compared with wild-type mice following S. rectivirgula exposure. The results from our studies suggest that one or more PRR(s) upstream of MyD88 are necessary for neutrophil recruitment following S. rectivirgula exposure.

AB - Hypersensitivity pneumonitis is an interstitial lung disease that is characterized by alveolitis, granuloma formation, and in some patients, fibrosis. Using the Saccharopolyspora rectivirgula animal model of Farmer's lung disease, our laboratory has demonstrated that neutrophils play a critical role in IFN-γ production during the acute phase of the disease. As IFN-γ is necessary for granuloma formation, it is important to identify the factors that lead to neutrophil recruitment during disease. To begin to identify the pattern recognition receptors (PRRs) that initiate chemokine production, leading to neutrophil recruitment following S. rectivirgula exposure, we examined the role of MyD88 and TLR2. Our results demonstrate that neutrophil recruitment, as measured by flow cytometry and the myeloperoxidase assay, was abolished in the absence of MyD88 following S. rectivirgula exposure. The decrease in neutrophil recruitment was likely a result of a significant decrease in production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine. These results suggest that S. rectivirgula interacts with PRRs that are upstream of the MyD88 pathway to initiate cytokine and chemokine production. In vitro studies suggest that S. rectivirgula can interact with TLR2, and stimulation of adherent cells from TLR2 knockout (KO) mice with S. rectivirgula resulted in a significant decrease in MIP-2 production. However, TLR2 KO mice did not have a reduction in neutrophil recruitment compared with wild-type mice following S. rectivirgula exposure. The results from our studies suggest that one or more PRR(s) upstream of MyD88 are necessary for neutrophil recruitment following S. rectivirgula exposure.

UR - http://www.scopus.com/inward/record.url?scp=46949094011&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46949094011&partnerID=8YFLogxK

U2 - 10.1189/jlb.0607391

DO - 10.1189/jlb.0607391

M3 - Article

VL - 83

SP - 1207

EP - 1217

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 5

ER -