Neutropenia alters lung cytokine production in mice and reduces their susceptibility to pulmonary cryptococcosis

Aron J. Mednick, Marta Feldmesser, Johanna Rivera, Arturo Casadevall

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Neutrophils are generally considered to contribute to host defense through their potent microbicidal activity. However, there is accumulating evidence that neutrophils also have an important regulatory role in establishing the balance of Th1 and Th2 responses. This study investigated the role of neutrophils in defense against pulmonary Cryptococcus neoformans infection using neutrophil-depleted BALB/c mice generated by administering mAb RB6-8C5. Neutropenic mice with pulmonary infection survived significantly longer than control mice, but there was no difference between groups infected intravenously. On day 1 of infection, neutropenic mice had significantly smaller fungal burdens than control mice. On day 7, neutropenic mice had significantly higher lung concentrations of IL-10, TNF-α, IL-4, and IL-12 than control mice, but there was no difference in IFN-γ and MCP-1 levels. Neutrophils influenced the outcome of cryptococcal infection in mice through mechanisms that did not involve a reduction in early fungal burden. The absence of neutrophils in lung tissue during the initial stages of infection appeared to alter the inflammatory response in a manner that was subsequently beneficial to the host. Higher levels of Th1- and Th2-associated cytokines in neutropenic mice could have simultaneously promoted a strong cellular response while reducing inflammatory damage to the lung. Our results support the emerging concept that neutrophils play an important function in modulating the development of the immune response.

Original languageEnglish (US)
Pages (from-to)1744-1753
Number of pages10
JournalEuropean Journal of Immunology
Volume33
Issue number6
DOIs
StatePublished - Jun 1 2003

Fingerprint

Cryptococcosis
Neutropenia
Cytokines
Neutrophils
Lung
Infection
Th1-Th2 Balance
Cryptococcus neoformans
Interleukin-12
Interleukin-4
Interleukin-10

Keywords

  • Cryptococcus neoformans
  • Fungus
  • Neutrophil
  • Pulmonary
  • RB6-8C5

ASJC Scopus subject areas

  • Immunology

Cite this

Neutropenia alters lung cytokine production in mice and reduces their susceptibility to pulmonary cryptococcosis. / Mednick, Aron J.; Feldmesser, Marta; Rivera, Johanna; Casadevall, Arturo.

In: European Journal of Immunology, Vol. 33, No. 6, 01.06.2003, p. 1744-1753.

Research output: Contribution to journalArticle

@article{5af1dfb804934a03b5fce3783dbf3c37,
title = "Neutropenia alters lung cytokine production in mice and reduces their susceptibility to pulmonary cryptococcosis",
abstract = "Neutrophils are generally considered to contribute to host defense through their potent microbicidal activity. However, there is accumulating evidence that neutrophils also have an important regulatory role in establishing the balance of Th1 and Th2 responses. This study investigated the role of neutrophils in defense against pulmonary Cryptococcus neoformans infection using neutrophil-depleted BALB/c mice generated by administering mAb RB6-8C5. Neutropenic mice with pulmonary infection survived significantly longer than control mice, but there was no difference between groups infected intravenously. On day 1 of infection, neutropenic mice had significantly smaller fungal burdens than control mice. On day 7, neutropenic mice had significantly higher lung concentrations of IL-10, TNF-α, IL-4, and IL-12 than control mice, but there was no difference in IFN-γ and MCP-1 levels. Neutrophils influenced the outcome of cryptococcal infection in mice through mechanisms that did not involve a reduction in early fungal burden. The absence of neutrophils in lung tissue during the initial stages of infection appeared to alter the inflammatory response in a manner that was subsequently beneficial to the host. Higher levels of Th1- and Th2-associated cytokines in neutropenic mice could have simultaneously promoted a strong cellular response while reducing inflammatory damage to the lung. Our results support the emerging concept that neutrophils play an important function in modulating the development of the immune response.",
keywords = "Cryptococcus neoformans, Fungus, Neutrophil, Pulmonary, RB6-8C5",
author = "Mednick, {Aron J.} and Marta Feldmesser and Johanna Rivera and Arturo Casadevall",
year = "2003",
month = "6",
day = "1",
doi = "10.1002/eji.200323626",
language = "English (US)",
volume = "33",
pages = "1744--1753",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "6",

}

TY - JOUR

T1 - Neutropenia alters lung cytokine production in mice and reduces their susceptibility to pulmonary cryptococcosis

AU - Mednick, Aron J.

AU - Feldmesser, Marta

AU - Rivera, Johanna

AU - Casadevall, Arturo

PY - 2003/6/1

Y1 - 2003/6/1

N2 - Neutrophils are generally considered to contribute to host defense through their potent microbicidal activity. However, there is accumulating evidence that neutrophils also have an important regulatory role in establishing the balance of Th1 and Th2 responses. This study investigated the role of neutrophils in defense against pulmonary Cryptococcus neoformans infection using neutrophil-depleted BALB/c mice generated by administering mAb RB6-8C5. Neutropenic mice with pulmonary infection survived significantly longer than control mice, but there was no difference between groups infected intravenously. On day 1 of infection, neutropenic mice had significantly smaller fungal burdens than control mice. On day 7, neutropenic mice had significantly higher lung concentrations of IL-10, TNF-α, IL-4, and IL-12 than control mice, but there was no difference in IFN-γ and MCP-1 levels. Neutrophils influenced the outcome of cryptococcal infection in mice through mechanisms that did not involve a reduction in early fungal burden. The absence of neutrophils in lung tissue during the initial stages of infection appeared to alter the inflammatory response in a manner that was subsequently beneficial to the host. Higher levels of Th1- and Th2-associated cytokines in neutropenic mice could have simultaneously promoted a strong cellular response while reducing inflammatory damage to the lung. Our results support the emerging concept that neutrophils play an important function in modulating the development of the immune response.

AB - Neutrophils are generally considered to contribute to host defense through their potent microbicidal activity. However, there is accumulating evidence that neutrophils also have an important regulatory role in establishing the balance of Th1 and Th2 responses. This study investigated the role of neutrophils in defense against pulmonary Cryptococcus neoformans infection using neutrophil-depleted BALB/c mice generated by administering mAb RB6-8C5. Neutropenic mice with pulmonary infection survived significantly longer than control mice, but there was no difference between groups infected intravenously. On day 1 of infection, neutropenic mice had significantly smaller fungal burdens than control mice. On day 7, neutropenic mice had significantly higher lung concentrations of IL-10, TNF-α, IL-4, and IL-12 than control mice, but there was no difference in IFN-γ and MCP-1 levels. Neutrophils influenced the outcome of cryptococcal infection in mice through mechanisms that did not involve a reduction in early fungal burden. The absence of neutrophils in lung tissue during the initial stages of infection appeared to alter the inflammatory response in a manner that was subsequently beneficial to the host. Higher levels of Th1- and Th2-associated cytokines in neutropenic mice could have simultaneously promoted a strong cellular response while reducing inflammatory damage to the lung. Our results support the emerging concept that neutrophils play an important function in modulating the development of the immune response.

KW - Cryptococcus neoformans

KW - Fungus

KW - Neutrophil

KW - Pulmonary

KW - RB6-8C5

UR - http://www.scopus.com/inward/record.url?scp=0038758881&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038758881&partnerID=8YFLogxK

U2 - 10.1002/eji.200323626

DO - 10.1002/eji.200323626

M3 - Article

VL - 33

SP - 1744

EP - 1753

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 6

ER -